< C i t e > < A u t h o r > K o n d o < / A u t h o r > < Y e a r > 2 0 0 3 < / Y e a r > < R e c N u m > 8 8 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 2 6 1 5 8 9 2 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 1 < / V O L U M E > < Y E A R > 2 0 0 3 < / Y E A R > < T I T L E > B i o l o g y o f h e m a t o p o i e t i c s t e m c e l l s a n d p r o g e n i t o r s : i m p l i c a t i o n s f o r c l i n i c a l a p p l i c a t i o n < / T I T L E > < P A G E S > 7 5 9 - 8 0 6 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f I m m u n o l o g y , D u k e U n i v e r s i t y M e d i c a l C e n t e r , D u r h a m , N o r t h C a r o l i n a 2 7 7 1 0 , U S A . m o t o n a r i . k o n d o @ d u k e . e d u < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > K o n d o , M . < / A U T H O R > < A U T H O R > W a g e r s , A . J . < / A U T H O R > < A U T H O R > M a n z , M . G . < / A U T H O R > < A U T H O R > P r o h a s k a , S . S . < / A U T H O R > < A U T H O R > S c h e r e r , D . C . < / A U T H O R > < A U T H O R > B e i l h a c k , G . F . < / A U T H O R > < A U T H O R > S h i z u r u , J . A . < / A U T H O R > < A U T H O R > W e i s s m a n , I . L . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > A n n u R e v I m m u n o l < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > A p o p t o s i s < / K E Y W O R D > < K E Y W O R D > A u t o i m m u n e D i s e a s e s / t h e r a p y < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n < / K E Y W O R D > < K E Y W O R D > C e l l M o v e m e n t < / K E Y W O R D > < K E Y W O R D > C e l l S e p a r a t i o n < / K E Y W O R D > < K E Y W O R D > D i a b e t e s M e l l i t u s , T y p e 1 / t h e r a p y < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n P r o f i l i n g < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e s i s < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l T r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / * c y t o l o g y / * i m m u n o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > N e o p l a s m s / t h e r a p y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 2 6 1 5 8 9 2 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > C o t t a < / A u t h o r > < Y e a r > 2 0 0 3 < / Y e a r > < R e c N u m > 8 3 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 2 5 6 0 2 2 1 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 0 1 < / V O L U M E > < N U M B E R > 1 1 < / N U M B E R > < Y E A R > 2 0 0 3 < / Y E A R > < D A T E > J u n 1 < / D A T E > < T I T L E > P a x 5 d e t e r m i n e s B - v e r s u s T - c e l l f a t e a n d d o e s n o t b l o c k e a r l y m y e l o i d - l i n e a g e d e v e l o p m e n t < / T I T L E > < P A G E S > 4 3 4 2 - 6 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f P a t h o l o g y , U n i v e r s i t y o f A l a b a m a a t B i r m i n g h a m , B i r m i n g h a m , A L 3 5 2 9 4 - 3 3 0 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > C o t t a , C . V . < / A U T H O R > < A U T H O R > Z h a n g , Z . < / A U T H O R > < A U T H O R > K i m , H . G . < / A U T H O R > < A U T H O R > K l u g , C . A . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B l o o d < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B - C e l l - S p e c i f i c A c t i v a t o r P r o t e i n < / K E Y W O R D > < K E Y W O R D > B - L y m p h o c y t e s / * c y t o l o g y / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > C e l l L i n e a g e / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > D N A - B i n d i n g P r o t e i n s / g e n e t i c s / p h a r m a c o l o g y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / c y t o l o g y / d r u g e f f e c t s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > K i l l e r C e l l s , N a t u r a l / c y t o l o g y / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > * L e u k o p o i e s i s / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C 5 7 B L < / K E Y W O R D > < K E Y W O R D > M u l t i p o t e n t S t e m C e l l s / * c y t o l o g y / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > M y e l o i d C e l l s / * c y t o l o g y / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > T - L y m p h o c y t e s / * c y t o l o g y / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > T r a n s c r i p t i o n F a c t o r s / g e n e t i c s / p h a r m a c o l o g y / * p h y s i o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 2 5 6 0 2 2 1 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 1 6 , 1 1 7 ) . O v a k v u s t r a t e g i j u n i j e m o g u e p r i m i j e n i t i n a s t a n i c e o s t e o p r o g e n i t o r s k e l o z e , d i j e l o m z b o g l o k a l i z a c i j e s t a n i c a u n u t a r s o l i d n e k o at a n e m e u s t a n i
n e t v a r i .
Z e l e n i f l u o r e s c e n t n i p r o t e i n p o d k o n t r o l o m p r o m o t o r a k o j i s e a k t i v i r a n a s p e c i f i
n o m s t a d i j u s t a n i
n e d i f e r e n c i j a c i j e , p r u ~a m o g u n o s t i d e n t i f i c i r a n j a i i z o l i r a n j a s u b p o p u l a c i j a s t a n i c a u r a z l i
i t i m s t a d i j i m a o s t e o b l a s t i
n o g r a z v o j a . U p r i m a r n i m s t a n i
n i m k u l t u r a m a p O B C o l 3 . 6 G F P s e a k t i v i r a s v r l o n i s k i m i n t e n z i t e t o m i s t o v r e m e n o s p o j a v o m a k t i v n o s t i a l k a l n e f o s f a t a z e ( A L P ) u s t a n i c a m a k o j e t v o r e p o
e t n i s t a d i j k o at a n o g
v o r i a A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > K a l a j z i c < / A u t h o r > < Y e a r > 2 0 0 2 < / Y e a r > < R e c N u m > 2 8 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 1 7 7 1 6 6 2 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 7 < / V O L U M E > < N U M B E R > 1 < / N U M B E R > < Y E A R > 2 0 0 2 < / Y E A R > < D A T E > J a n < / D A T E > < T I T L E > U s e o f t y p e I c o l l a g e n g r e e n f l u o r e s c e n t p r o t e i n t r a n s g e n e s t o i d e n t i f y s u b p o p u l a t i o n s o f c e l l s a t d i f f e r e n t s t a g e s o f t h e o s t e o b l a s t l i n e a g e < / T I T L E > < P A G E S > 1 5 - 2 5 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n 0 6 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > K a l a j z i c , I . < / A U T H O R > < A U T H O R > K a l a j z i c , Z . < / A U T H O R > < A U T H O R > K a l i t e r n a , M . < / A U T H O R > < A U T H O R > G r o n o w i c z , G . < / A U T H O R > < A U T H O R > C l a r k , S . H . < / A U T H O R > < A U T H O R > L i c h t l e r , A . C . < / A U T H O R > < A U T H O R > R o w e , D . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J B o n e M i n e r R e s < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B o n e a n d B o n e s / c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C o l l a g e n T y p e I / * g e n e t i c s < / K E Y W O R D > < K E Y W O R D > F e m u r / c y t o l o g y / g r o w t h & a m p ; d e v e l o p m e n t / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n R e g u l a t i o n , D e v e l o p m e n t a l < / K E Y W O R D > < K E Y W O R D > G r e e n F l u o r e s c e n t P r o t e i n s < / K E Y W O R D > < K E Y W O R D > L u m i n e s c e n t P r o t e i n s / * g e n e t i c s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / * c l a s s i f i c a t i o n / c y t o l o g y / * m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > P r o m o t e r R e g i o n s ( G e n e t i c s ) < / K E Y W O R D > < K E Y W O R D > R N A , M e s s e n g e r / g e n e t i c s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R a t s < / K E Y W O R D > < K E Y W O R D > R e c o m b i n a n t P r o t e i n s / g e n e t i c s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > T e n d o n s / c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > T i s s u e D i s t r i b u t i o n < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 1 7 7 1 6 6 2 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 9 7 ) . M i k r o
i p a n a l i z a s t a n i c a o d v o j e n i h f l u o r e s c e n t n o m p r o t o
n o m c i t o m e t r i j o m p o k a z u j e d a G F P s t a n i c e g u b e i z r a ~a j g e n a k a r a k t e r i s t i
n i h z a p e r i c i t / m i o f i b r o b l a s t , u k a z u j u i d a s e r a n e p r o g e n i t o r s k e s t a n i c e u n u t a r G F P n e g a t i v n e p o p u l a c i j e p r e d o d r e u j u z a o s t e o b l a s t i
n u l o z u A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > K a l a j z i c < / A u t h o r > < Y e a r > 2 0 0 5 < / Y e a r > < R e c N u m > 1 3 5 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 8 3 4 1 3 6 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 8 0 < / V O L U M E > < N U M B E R > 2 6 < / N U M B E R > < Y E A R > 2 0 0 5 < / Y E A R > < D A T E > J u l 1 < / D A T E > < T I T L E > E x p r e s s i o n p r o f i l e o f o s t e o b l a s t l i n e a g e a t d e f i n e d s t a g e s o f d i f f e r e n t i a t i o n < / T I T L E > < P A G E S > 2 4 6 1 8 - 2 6 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n , C o n n e c t i c u t 0 6 0 5 3 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > K a l a j z i c , I . < / A U T H O R > < A U T H O R > S t a a l , A . < / A U T H O R > < A U T H O R > Y a n g , W . P . < / A U T H O R > < A U T H O R > W u , Y . < / A U T H O R > < A U T H O R > J o h n s o n , S . E . < / A U T H O R > < A U T H O R > F e y e n , J . H . < / A U T H O R > < A U T H O R > K r u e g e r , W . < / A U T H O R > < A U T H O R > M a y e , P . < / A U T H O R > < A U T H O R > Y u , F . < / A U T H O R > < A U T H O R > Z h a o , Y . < / A U T H O R > < A U T H O R > K u o , L . < / A U T H O R > < A U T H O R > G u p t a , R . R . < / A U T H O R > < A U T H O R > A c h e n i e , L . E . < / A U T H O R > < A U T H O R > W a n g , H . W . < / A U T H O R > < A U T H O R > S h i n , D . G . < / A U T H O R > < A U T H O R > R o w e , D . W . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J B i o l C h e m < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B l o t t i n g , N o r t h e r n < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l L i n e a g e < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n P r o f i l i n g / m e t h o d s < / K E Y W O R D > < K E Y W O R D > * G e n e E x p r e s s i o n R e g u l a t i o n < / K E Y W O R D > < K E Y W O R D > * G e n e E x p r e s s i o n R e g u l a t i o n , D e v e l o p m e n t a l < / K E Y W O R D > < K E Y W O R D > G r e e n F l u o r e s c e n t P r o t e i n s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > O l i g o n u c l e o t i d e A r r a y S e q u e n c e A n a l y s i s < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / * c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > O s t e o c l a s t s / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > O s t e o g e n e s i s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > P r o m o t e r R e g i o n s ( G e n e t i c s ) < / K E Y W O R D > < K E Y W O R D > R N A / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R N A , M e s s e n g e r / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N . I . H . , E x t r a m u r a l < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S i g n a l T r a n s d u c t i o n < / K E Y W O R D > < K E Y W O R D > T i m e F a c t o r s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 8 3 4 1 3 6 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 1 8 ) . H i s t o l o ak a a n a l i z a k o s t i p o k a z u j e f i b r o b l a s t i
n e s t a n i c e s m j e at e n e n a p e r i o s t e u m u s n i s k i m i n t e n z i t e t o m G F P i z a ~a j a . N a t e m e l j u s t a n i
n i h k u l t u r a i h i s t o l o ak i h p o d a t a k a , n i s k i i n t e n z i t e t i z r a ~a j a p O B C o l 3 . 6 G F P - a m o ~e s e p o v e z a t i s p r e o s t e o b l a s t i
n i m s t a d i j e m d i f e r e n c i j a c i j e .
T a k o e r j e u t v r e n a p o v e z a n o s t i z r a ~a j a p O B C o l 3 . 6 G F P - a j a k o g i n t e n z i t e t a i p O B C o l 2 . 3 G F P - a s a z r e l i m o s t e o b l a s t i m a A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > K a l a j z i c < / A u t h o r > < Y e a r > 2 0 0 2 < / Y e a r > < R e c N u m > 2 8 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 1 7 7 1 6 6 2 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 7 < / V O L U M E > < N U M B E R > 1 < / N U M B E R > < Y E A R > 2 0 0 2 < / Y E A R > < D A T E > J a n < / D A T E > < T I T L E > U s e o f t y p e I c o l l a g e n g r e e n f l u o r e s c e n t p r o t e i n t r a n s g e n e s t o i d e n t i f y s u b p o p u l a t i o n s o f c e l l s a t d i f f e r e n t s t a g e s o f t h e o s t e o b l a s t l i n e a g e < / T I T L E > < P A G E S > 1 5 - 2 5 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n 0 6 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > K a l a j z i c , I . < / A U T H O R > < A U T H O R > K a l a j z i c , Z . < / A U T H O R > < A U T H O R > K a l i t e r n a , M . < / A U T H O R > < A U T H O R > G r o n o w i c z , G . < / A U T H O R > < A U T H O R > C l a r k , S . H . < / A U T H O R > < A U T H O R > L i c h t l e r , A . C . < / A U T H O R > < A U T H O R > R o w e , D . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J B o n e M i n e r R e s < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B o n e a n d B o n e s / c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C o l l a g e n T y p e I / * g e n e t i c s < / K E Y W O R D > < K E Y W O R D > F e m u r / c y t o l o g y / g r o w t h & a m p ; d e v e l o p m e n t / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n R e g u l a t i o n , D e v e l o p m e n t a l < / K E Y W O R D > < K E Y W O R D > G r e e n F l u o r e s c e n t P r o t e i n s < / K E Y W O R D > < K E Y W O R D > L u m i n e s c e n t P r o t e i n s / * g e n e t i c s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / * c l a s s i f i c a t i o n / c y t o l o g y / * m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > P r o m o t e r R e g i o n s ( G e n e t i c s ) < / K E Y W O R D > < K E Y W O R D > R N A , M e s s e n g e r / g e n e t i c s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R a t s < / K E Y W O R D > < K E Y W O R D > R e c o m b i n a n t P r o t e i n s / g e n e t i c s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > T e n d o n s / c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > T i s s u e D i s t r i b u t i o n < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 1 7 7 1 6 6 2 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 9 7 ) . O v e s u s t a n i c e u v i j e k p o v e z a n e s m i n e r a l i z i r a n i m
v o r i e m i n v i t r o i m i n e r a l i z i r a n i m m a t r i k s o m i n v i v o . M i k r o
i p a n a l i z a p O B C o l 2 . 3 G F P p o z i t i v n i h s t a n i c a i z o l i r a n i h p r o t o
n o m c i t o m e t r i j o m p o k a z u j e s n a ~n i i z r a ~a j o s t e o b l a s t - s p e c i f i
n i h g e n a u u s p o r e d b i s p O B C o l 2 . 3 G F P n e g a t i v n o m p o p u l a c i j o m i z i s t e k u l t u r e A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > K a l a j z i c < / A u t h o r > < Y e a r > 2 0 0 5 < / Y e a r > < R e c N u m > 1 3 5 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 8 3 4 1 3 6 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 8 0 < / V O L U M E > < N U M B E R > 2 6 < / N U M B E R > < Y E A R > 2 0 0 5 < / Y E A R > < D A T E > J u l 1 < / D A T E > < T I T L E > E x p r e s s i o n p r o f i l e o f o s t e o b l a s t l i n e a g e a t d e f i n e d s t a g e s o f d i f f e r e n t i a t i o n < / T I T L E > < P A G E S > 2 4 6 1 8 - 2 6 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n , C o n n e c t i c u t 0 6 0 5 3 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > K a l a j z i c , I . < / A U T H O R > < A U T H O R > S t a a l , A . < / A U T H O R > < A U T H O R > Y a n g , W . P . < / A U T H O R > < A U T H O R > W u , Y . < / A U T H O R > < A U T H O R > J o h n s o n , S . E . < / A U T H O R > < A U T H O R > F e y e n , J . H . < / A U T H O R > < A U T H O R > K r u e g e r , W . < / A U T H O R > < A U T H O R > M a y e , P . < / A U T H O R > < A U T H O R > Y u , F . < / A U T H O R > < A U T H O R > Z h a o , Y . < / A U T H O R > < A U T H O R > K u o , L . < / A U T H O R > < A U T H O R > G u p t a , R . R . < / A U T H O R > < A U T H O R > A c h e n i e , L . E . < / A U T H O R > < A U T H O R > W a n g , H . W . < / A U T H O R > < A U T H O R > S h i n , D . G . < / A U T H O R > < A U T H O R > R o w e , D . W . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J B i o l C h e m < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B l o t t i n g , N o r t h e r n < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l L i n e a g e < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n P r o f i l i n g / m e t h o d s < / K E Y W O R D > < K E Y W O R D > * G e n e E x p r e s s i o n R e g u l a t i o n < / K E Y W O R D > < K E Y W O R D > * G e n e E x p r e s s i o n R e g u l a t i o n , D e v e l o p m e n t a l < / K E Y W O R D > < K E Y W O R D > G r e e n F l u o r e s c e n t P r o t e i n s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > O l i g o n u c l e o t i d e A r r a y S e q u e n c e A n a l y s i s < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / * c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > O s t e o c l a s t s / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > O s t e o g e n e s i s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > P r o m o t e r R e g i o n s ( G e n e t i c s ) < / K E Y W O R D > < K E Y W O R D > R N A / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R N A , M e s s e n g e r / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N . I . H . , E x t r a m u r a l < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S i g n a l T r a n s d u c t i o n < / K E Y W O R D > < K E Y W O R D > T i m e F a c t o r s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 8 3 4 1 3 6 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 1 8 ) . J e d a n o d n e d o s t a t a k a p O B C o l 2 . 3 G F P b i l j e g a j e s t n j e g o v i z r a ~a j u v e i n i o s t e o c i t a t a k o d a j e n e m o g u e r a z l i k o v a t i z r e l e o s t e o b l a s t e o d o s t e o c i t a . I p a k , t a j p r o b l e m j e r i j e ae n r a z v o j e m D M P 1 - G F P m i aa
i j i j e i z r a ~a j o g r a n i
e n n a p o p u l a c i j u s t a n i c a p r e o s t e o c i t a ( s t a n i c e o s t e o b l a s t i
n e l o z e k o j e s u u p r o c e s u u k l a p a n j a u k o at a n i m a t r i k s ) i o s t e o c i t a A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > K a l a j z i c < / A u t h o r > < Y e a r > 2 0 0 4 < / Y e a r > < R e c N u m > 8 7 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 2 0 7 7 4 3 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 3 5 < / V O L U M E > < N U M B E R > 1 < / N U M B E R > < Y E A R > 2 0 0 4 < / Y E A R > < D A T E > J u l < / D A T E > < T I T L E > D e n t i n m a t r i x p r o t e i n 1 e x p r e s s i o n d u r i n g o s t e o b l a s t i c d i f f e r e n t i a t i o n , g e n e r a t i o n o f a n o s t e o c y t e G F P - t r a n s g e n e < / T I T L E > < P A G E S > 7 4 - 8 2 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n 0 6 0 3 0 , U S A . i k a l a j @ n e u r o n . u c h c . e d u < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > K a l a j z i c , I . < / A U T H O R > < A U T H O R > B r a u t , A . < / A U T H O R > < A U T H O R > G u o , D . < / A U T H O R > < A U T H O R > J i a n g , X . < / A U T H O R > < A U T H O R > K r o n e n b e r g , M . S . < / A U T H O R > < A U T H O R > M i n a , M . < / A U T H O R > < A U T H O R > H a r r i s , M . A . < / A U T H O R > < A U T H O R > H a r r i s , S . E . < / A U T H O R > < A U T H O R > R o w e , D . W . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B o n e < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B o n e a n d B o n e s / c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > * C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l L i n e a g e < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > E x t r a c e l l u l a r M a t r i x P r o t e i n s / * b i o s y n t h e s i s / g e n e t i c s < / K E Y W O R D > < K E Y W O R D > G r e e n F l u o r e s c e n t P r o t e i n s / g e n e t i c s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / c y t o l o g y / * m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > O s t e o c y t e s / c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R N A , M e s s e n g e r / b i o s y n t h e s i s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N . I . H . , E x t r a m u r a l < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / c y t o l o g y / m e t a b o l i s m < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 2 0 7 7 4 3 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 1 9 ) . J e d a n r a z l o g z a r a z v o j h O C - G F P m i aj e l i n i j e j e s t m o g u n o s t u ~e p o d j e l e p o p u l a c i j e p O B C o l 2 . 3 G F P p o z i t i v n i h s t a n i c a . S p e c i f i
n o , d a l i s t a n i c e n a p o v r ai n i k o s t i p o k a z u j u r a z l i
i t e s t a d i j e o s t e o b l a s t i
n e d i f e r e n c i j a c i j e k o j e n e m o ~e m o v i d j e t i s a s t a n d a r d n o m h i s t o l o g i j o m , n i t i s o s t e o b l a s t i
n i m G F P b i l j e g - g e n o m ai r e g s p e k t r a ?
1 . 2 . U p o r a b a h O C - G F P t r a n s g e n i
n i h m i ae v a p r i o b i l j e ~a v a n j u p o p u l a c i j e z r e l i h o s t e o b l a s t a
D v i j e h O C - G F P t p z m i aj e l i n i j e n a p r a v l j e n e s h u m a n i m 3 . 8 k b p r o m o t o r s k i m f r a g m e n t o m , i m a j u s n a g u i v j e r o d o s t o j n o s t v i z u a l n o g b i l j e g a o s t e o b l a s t a s i z r a ~a j e m o s t e o k a l c i n a . Z r e l i o s t e o b l a s t i s u o b i l j e ~e n i o v i m k o n s t r u k t o m j e r j e n j e g o v i z r a ~a j o g r a n i
e n n a s t a n i c e u n u t a r d o b r o r a z v i j e n o g a k o at a n o g
v o r i a u i n v i t r o u v j e t i m a , d o k s t a n i c e i z o l i r a n e p r o t o
n o m c i t o m e t r i j o m s n a ~n o i z r a ~a v a j u e n d o g e n i o s t e o k a l c i n u o d n o s u n a G F P n e g a t i v n u p o p u l a c i j u i z i s t e k u l t u r e . N a d a l j e , i n s i t u h i b r i d i z a c i j a k o s t i i z u b a p o k a z u j e k o - l o k a l i z a c i j u s t a n i c a p o z i t i v n i h n a m R N A e n d o g e n o g o s t e o k a l c i n a i h O C - G F P t p z t r a n s g e n .
G F P s i g n a l s e d o b r o z a d r ~a v a u d e k a l c i n i r a n i m i n e d e k a l c i n i r a n i m s m r z n u t i m r e z o v i m a k o s t i t e j e m o g u e p o v e z a t i i z r a ~a j u i n v i t r o s i z r a ~a j e m u i n t a k t n o j k o s t i . K a o at o s e i o
e k i v a l o , u n e z r e l i m o s t e o b l a s t i m a p r i m a r n e s p o n g i o z e n e m a h O C - G F P t p z i z r a ~a j a , o s i m u n e k o l i c i n i h i p e r t r o f i
n i h h o n d r o c i t a . U p r i j a an j i m s t u d i j a m a p o k a z a n o j e d a h i p e r t r o f i
n i h o n d r o c i t i u n u t a r m i n e r a l i z i r a j u e g m a t r i k s a p r i l i k o m o k o at a v a n j a p o p r i m a j u f e n o t i p s k e b i l j e g e o s t e o b l a s t a k a o at o s u i z r a ~a j o s t e o k a l c i n a i o s t e o p o n t i n a A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > L i a n < / A u t h o r > < Y e a r > 1 9 9 3 < / Y e a r > < R e c N u m > 1 4 4 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 8 3 6 6 1 3 7 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 5 2 < / V O L U M E > < N U M B E R > 2 < / N U M B E R > < Y E A R > 1 9 9 3 < / Y E A R > < D A T E > J u n < / D A T E > < T I T L E > I n d u c t i o n o f b o n e - r e l a t e d p r o t e i n s , o s t e o c a l c i n a n d o s t e o p o n t i n , a n d t h e i r m a t r i x u l t r a s t r u c t u r a l l o c a l i z a t i o n w i t h d e v e l o p m e n t o f c h o n d r o c y t e h y p e r t r o p h y i n v i t r o < / T I T L E > < P A G E S > 2 0 6 - 1 9 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f C e l l B i o l o g y , U n i v e r s i t y o f M a s s a c h u s e t t s M e d i c a l C e n t e r , W o r c e s t e r 0 1 6 5 5 . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > L i a n , J . B . < / A U T H O R > < A U T H O R > M c K e e , M . D . < / A U T H O R > < A U T H O R > T o d d , A . M . < / A U T H O R > < A U T H O R > G e r s t e n f e l d , L . C . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J C e l l B i o c h e m < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B l o t t i n g , W e s t e r n < / K E Y W O R D > < K E Y W O R D > B o n e M a t r i x / m e t a b o l i s m / * u l t r a s t r u c t u r e < / K E Y W O R D > < K E Y W O R D > C a l c i u m / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > C a r t i l a g e / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C h i c k E m b r y o < / K E Y W O R D > < K E Y W O R D > H y p e r t r o p h y < / K E Y W O R D > < K E Y W O R D > M i c r o s c o p y , E l e c t r o n < / K E Y W O R D > < K E Y W O R D > O s t e o c a l c i n / * b i o s y n t h e s i s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S i a l o g l y c o p r o t e i n s / * b i o s y n t h e s i s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 8 3 6 6 1 3 7 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 2 0 ) . S m a t r a s e d a o v o p r e d s t a v l j a u z n a p r e d o v a l i s t a d i j h o n d r o c i t n e h i p e r t r o f i j e i l i t r a n s - d i f e r e n c i j a c i j u h o n d r o c i t a u o s t e o b l a s t . S t a n i c e n a e n d o s t e a l n o j p o v r ai n i d i j a f i z e p o k a z u j u j a k u f l u o r e s c e n c i j u . P o s t o j i j a k a p o v e z a n o s t i z m e u h O C - G F P t p z p o z i t i v n i h s t a n i c a n a p o v r ai n i i s v j e ~e s t v o r e n o g a k o at a n o g m a t r i k s a , u k a z u j u i d a s u o s t e o k a l c i n s k i m p r o m o t o r o m o b i l j e ~e n e o n e s t a n i c e k o j e a k t i v n o s t v a r a j u m a t r i k s . D o b ~i v o t i n j e o s o b i t o j e v a ~n a z a i z r a ~a j o v o g t r a n s g e n a . U f e m u r u 7 d a n a s t a r i h m i ae v a , G F P t p z p o z i t i v n e s t a n i c e s u p r i s u t n e n a e n d o s t e a l n o j p o v r ai n i i u k o r t i k a l n o j k o s t i , d o k s u u d o b i o d j e d n o g m j e s e c a p o z i t i v n i s a m o n e d a v n o s t v o r e n i o s t e o c i t i . U 3 . i 6 . m j e s e c u s t a r o s t i , o s t e o c i t i u n u t a r k o r t i k a l n e k o s t i n i s u o b i l j e ~e n i G F P - o m i z u z e v s t a n i c a u z o n a m a a k t i v n e k o at a n e p r e g r a d n j e , d o k i n t e n z i v n o p o z i t i v n e G F P o s t e o b l a s t e n a l a z i m o d u ~ o d r e e n o g d i j e l a p e r i o s t e a l n e p o v r ai n e . S l i j e d G F P p o z i t i v n i h s t a n i c a p o
i n j e n a g l o u p o d r u
j u z g l o b n e h r s k a v i c e , n a s t a v l j a s e d u ~ m e t a f i z n e r e g i j e i z a v r aa v a p r i j e p o
e t k a d i j a f i z e . S t u d i j e n a p r a v l j e n e n a l j u d s k i m f e m u r i m a u s t a r i j o j d o b i p o k a z a l e s u p r i s u s t v o v e l i k e m i n e r a l i z i r a n e p o v r ai n e n a p e r i o s t e a l n o j p o v r ai n i f e m o r a l n o g v r a t a , k o j a s e s a s t o j i o d g u s t i h k a c i f i c i r a n i h a g r e g a t a b e z o s t e o c i t n i h l a k u n a A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > Z a g b a - M o n g a l i m a < / A u t h o r > < Y e a r > 1 9 8 8 < / Y e a r > < R e c N u m > 1 4 8 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 3 2 2 0 2 6 2 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 3 4 < / V O L U M E > < N U M B E R > 5 - 6 < / N U M B E R > < Y E A R > 1 9 8 8 < / Y E A R > < T I T L E > A g e c h a n g e s i n h u m a n b o n e : a m i c r o r a d i o g r a p h i c a n d h i s t o l o g i c a l s t u d y o f s u b p e r i o s t e a l a n d p e r i o s t e a l c a l c i f i c a t i o n s < / T I T L E > < P A G E S > 2 6 4 - 7 6 < / P A G E S > < A U T H O R _ A D D R E S S > U n i t o f H u m a n A n a t o m y , F a c u l t y o f M e d i c i n e , C a t h o l i c U n i v e r s i t y o f L o u v a i n , B e l g i u m . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > Z a g b a - M o n g a l i m a , G . < / A U T H O R > < A U T H O R > G o r e t - N i c a i s e , M . < / A U T H O R > < A U T H O R > D h e m , A . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > G e r o n t o l o g y < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A d u l t < / K E Y W O R D > < K E Y W O R D > A g e d < / K E Y W O R D > < K E Y W O R D > A g e d , 8 0 a n d o v e r < / K E Y W O R D > < K E Y W O R D > A g i n g / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > B o n e D e v e l o p m e n t < / K E Y W O R D > < K E Y W O R D > B o n e a n d B o n e s / * a n a t o m y & a m p ; h i s t o l o g y < / K E Y W O R D > < K E Y W O R D > C a l c i f i c a t i o n , P h y s i o l o g i c < / K E Y W O R D > < K E Y W O R D > C o m p a r a t i v e S t u d y < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > M i c r o r a d i o g r a p h y < / K E Y W O R D > < K E Y W O R D > M i d d l e A g e d < / K E Y W O R D > < K E Y W O R D > P e r i o s t e u m / a n a t o m y & a m p ; h i s t o l o g y < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 3 2 2 0 2 6 2 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > A l l e n < / A u t h o r > < Y e a r > 2 0 0 5 < / Y e a r > < R e c N u m > 1 4 9 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 7 8 0 9 5 7 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 3 6 < / V O L U M E > < N U M B E R > 2 < / N U M B E R > < Y E A R > 2 0 0 5 < / Y E A R > < D A T E > F e b < / D A T E > < T I T L E > H u m a n f e m o r a l n e c k h a s l e s s c e l l u l a r p e r i o s t e u m , a n d m o r e m i n e r a l i z e d p e r i o s t e u m , t h a n f e m o r a l d i a p h y s e a l b o n e < / T I T L E > < P A G E S > 3 1 1 - 6 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f A n a t o m y a n d C e l l B i o l o g y , I n d i a n a U n i v e r s i t y S c h o o l o f M e d i c i n e , 6 3 5 B a r n h i l l D r i v e , M S - 5 0 3 5 I n d i a n a p o l i s , I N 4 6 2 0 2 , U S A . m a t a l l e n @ i u p u i . e d u < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > A l l e n , M . R . < / A U T H O R > < A U T H O R > B u r r , D . B . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B o n e < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A d u l t < / K E Y W O R D > < K E Y W O R D > A g e d < / K E Y W O R D > < K E Y W O R D > A g e d , 8 0 a n d o v e r < / K E Y W O R D > < K E Y W O R D > B o n e D e n s i t y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C a l c i f i c a t i o n , P h y s i o l o g i c / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C o m p a r a t i v e S t u d y < / K E Y W O R D > < K E Y W O R D > D i a p h y s e s / c y t o l o g y / p a t h o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > F e m u r / c y t o l o g y / p a t h o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > F e m u r N e c k / c y t o l o g y / m e t a b o l i s m / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > M i d d l e A g e d < / K E Y W O R D > < K E Y W O R D > P e r i o s t e u m / c y t o l o g y / p a t h o l o g y / * p h y s i o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 7 8 0 9 5 7 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 2 1 , 1 2 2 ) . O v a m i n e r a l i z i r a n a p o v r ai n a n a s t a j e k a l c i f i c i r a n j e m f i b r o z n e i h i j a l i n e h r s k a v i c e A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > V a j d a < / A u t h o r > < Y e a r > 1 9 9 9 < / Y e a r > < R e c N u m > 1 4 7 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 0 3 5 9 5 2 1 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 5 5 < / V O L U M E > < N U M B E R > 2 < / N U M B E R > < Y E A R > 1 9 9 9 < / Y E A R > < D A T E > J u n 1 < / D A T E > < T I T L E > A g e - r e l a t e d h y p e r m i n e r a l i z a t i o n i n t h e f e m a l e p r o x i m a l h u m a n f e m u r < / T I T L E > < P A G E S > 2 0 2 - 1 1 < / P A G E S > < A U T H O R _ A D D R E S S > B o n e a n d J o i n t R e s e a r c h L a b o r a t o r y , V A M e d i c a l C e n t e r , S a l t L a k e C i t y , U t a h 8 4 1 4 8 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > V a j d a , E . G . < / A U T H O R > < A U T H O R > B l o e b a u m , R . D . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > A n a t R e c < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A d o l e s c e n t < / K E Y W O R D > < K E Y W O R D > A d u l t < / K E Y W O R D > < K E Y W O R D > A g e d < / K E Y W O R D > < K E Y W O R D > A g e d , 8 0 a n d o v e r < / K E Y W O R D > < K E Y W O R D > A g i n g / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > * C a l c i f i c a t i o n , P h y s i o l o g i c < / K E Y W O R D > < K E Y W O R D > C o m p a r a t i v e S t u d y < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > F e m u r / * p h y s i o l o g y / u l t r a s t r u c t u r e < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > I m a g e P r o c e s s i n g , C o m p u t e r - A s s i s t e d < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > M i c r o s c o p y , E l e c t r o n , S c a n n i n g < / K E Y W O R D > < K E Y W O R D > M i d d l e A g e d < / K E Y W O R D > < K E Y W O R D > P o s t m e n o p a u s e < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , N o n - P . H . S . < / K E Y W O R D > < K E Y W O R D > S e x C h a r a c t e r i s t i c s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 0 3 5 9 5 2 1 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > S h e a < / A u t h o r > < Y e a r > 2 0 0 1 < / Y e a r > < R e c N u m > 1 4 6 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 1 2 7 3 0 4 0 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 9 8 < / V O L U M E > < N U M B E R > P t 2 < / N U M B E R > < Y E A R > 2 0 0 1 < / Y E A R > < D A T E > F e b < / D A T E > < T I T L E > E v i d e n c e o f a h y p e r m i n e r a l i s e d c a l c i f i e d f i b r o c a r t i l a g e o n t h e h u m a n f e m o r a l n e c k a n d l e s s e r t r o c h a n t e r < / T I T L E > < P A G E S > 1 5 3 - 6 2 < / P A G E S > < A U T H O R _ A D D R E S S > B o n e a n d J o i n t R e s e a r c h L a b o r a t o r y , V A M e d i c a l C e n t e r , S a l t L a k e C i t y , U T 8 4 1 4 8 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > S h e a , J . E . < / A U T H O R > < A U T H O R > V a j d a , E . G . < / A U T H O R > < A U T H O R > B l o e b a u m , R . D . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J A n a t < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > C a r t i l a g e / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > C h o n d r o c a l c i n o s i s / c o m p l i c a t i o n s / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > F e m o r a l N e c k F r a c t u r e s / c o m p l i c a t i o n s / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > F e m u r / p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > F e m u r N e c k / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > * I m a g e P r o c e s s i n g , C o m p u t e r - A s s i s t e d < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > * M i c r o s c o p y , E l e c t r o n , S c a n n i n g < / K E Y W O R D > < K E Y W O R D > M i d d l e A g e d < / K E Y W O R D > < K E Y W O R D > P a t e l l a / p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , N o n - P . H . S . < / K E Y W O R D > < K E Y W O R D > S t a t i s t i c s , N o n p a r a m e t r i c < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 1 2 7 3 0 4 0 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 2 3 , 1 2 4 ) . K a o at o j e v e i s t a k n u t o , h i p e r t r o f i
n i h o n d r o c i t i i z r a ~a v a j u o s t e o k a l c i n u d o d i r u s m i n e r a l i z i r a n i m m a t r i k s o m , t e b i s e o v a k o m o g l o o b j a s n i t i p r i s u s t v o G F P p o z i t i v n i h p e r i o s t e a l n i h s t a n i c a b e z o d g o v a r a j u i h p o z i t i v n i h o s t e o c i t a i n j i h o v a n e p o v e z a n o s t s X O b o j a n j e m .
1 . 3 . U p o r a b a p O B C o l 3 . 6 G F P c y a n t r a n s g e n i
n i h m i ae v a p r i o b i l j e ~a v a n j u p o p u l a c i j e p r e o s t e o b l a s t a
P r o d u k c i j a p O B C o l 3 . 6 G F P c y a n t r a n s g e n a o m o g u i l a j e o b i l j e ~a v a n j e s t a n i c a o s t e o b l a s t i
n e l o z e u r a n o j r a z v o j n o j f a z i ( t z v . p r e o s t e o b l a s t i ) s a c y a n v a r i j a n t o m G F P - a . K r i ~a n j e m t r a n s g e n i
n i h m i ae v a p o z i t i v n i h n a j e d a n o d d v a t r a n s g e n a s r a z l i
i t i m G F P i z o m e r i m a ( p O B C o l 3 . 6 G F P c y a n i h O C - G F P t o p a z ) d o p u s t i t e n a m r a z l i k o v a n j e r a z l i
i t i h s t a d i j a d i f e r e n c i j a c i j e o s t e o b l a s t a u i s t i m e k s p e r i m e n t a l n i m s i s t e m i m a , s t a n i
n i m k u l t u r a m a i h i s t o l o ak i m r e z o v i m a k o s t i .
p O B C o l 3 . 6 G F P c y a n t r a n s g e n i
n e ~i v o t i n j e t a k o e r p o k a z u j u i z r a ~a j o v i s a n o d o b i . Z a r a z l i k u o d h O C - G F P t p z - a , n j e g o v s e n a j j a
i i z r a ~a j o p a ~a u p r i m a r n o j s p o n g i o z i 8 d a n a s t a r i h m i ae v a . I p a k , k a s n i j e o b a t r a n s g e n a p o k a z u j u s l i
a n i z r a ~a j k o j i o d r a ~a v a s t v a r a n j e n o v e k o s t i u r e l a t i v n o m l a d i h ~i v o t i n j a i k o at a n u p r e g r a d n j u u s t a r i j i h m i ae v a . U 1 m j e s e c s t a r i m m i ae v i m a s n a ~a n i z r a ~a j t r a n s g e n a s e v i d i n a p o v r ai n i t r a b e k u l a r n e i k o r t i k a l n e k o s t i . U 3 . i 5 . m j e s e c u s t a r o s t i , a k t i v n o s t j e o g r a n i
e n a n a p o v r ai n s k e s t a n i c e u p o d r u
j i m a e n d o s t e a l n e i t r a b e k u l a r n e k o s t i , t e j e n e m a u s t a n i c a m a u n u t a r m a t r i k s a .
1 . 4 . P r o c j e n a h e t e r o g e n o s t i p o p u l a c i j e o s t e o b l a s t a p o m o u p O B C o l 3 . 6 G F P c y a n X h O C - G F P t p z t r a n s g e n i
n i h m i ae v a
K a d a s e d v a b i l j e g a g e n a k r i ~a j u , v i d e s e t r i r a z l i
i t a s t a d i j a o s t e o b l a s t i
n e d i f e r e n c i j a c i j e . P r v e s u s t a n i c e , k o j e u p r i m a r n i m k u l t u r a m a b i v a j u z a m i j e e n e k a o p O B C o l 3 . 6 G F P c y a n p o z i t i v n e s t a n i c e s l a b o g i n t e n z i t e t a , a s a s a z r i j e v a n j e m p o p r i m a j u s v e j a
i i n t e n z i t e t i s t o g t r a n s g e n a , at o j e p o p r a e n o s a k t i v a c i j o m h O C - G F P t p z b i l j e g a . O v e s u s t a n i c e k u b o i d n e i s m j e at e n e u n u t a r m i n e r a l i z i r a j u e r e g i j e k o at a n o g a
v o r i a . S l i
n e s t a n i c e u i n t a k t n o j k o s t i k o j e i z r a ~a v a j u o b a t r a n s g e n a s m j e at e n e s u n a m j e s t i m a a k t i v n o g s t v a r a n j a n a p o v r ai n i k o s t i i u p r o s t o r i m a k o at a n e s r ~i u k o r t i k a l n o j k o s t i . D r u g o s u s t a n i c e k o j e i m a j u j a k i z r a ~a j p O B C o l 3 . 6 G F P c y a n b i l j e g a , b e z a k t i v a c i j e h O C - G F P t p z t r a n s g e n a . O v e s t a n i c e s m j e at e n e s u u i o k o l o m i n e r a l i z i r a j u e g k o at a n o g
v o r i a u p r i m a r n i m B M S C i m C O B k u l t u r a m a , t e s e u k o s t i n a l a z e n a m j e s t i m a n o v e o s t e o b l a s t i
n e d i f e r e n c i j a c i j e , p r i m a r n o u m e t a f i z a m a . T r e a j e p o p u l a c i j a s t a n i c a p r e d s t a v l j e n a s l a b i m p O B C o l 3 . 6 G F P c y a n i z r a ~a j e m k o j e u v r i j e m e a k t i v a c i j e h O C - G F P t p z t r a n s g e n a n e m a j a k u G F P c y a n e k s p r e s i j u . O v e s t a n i c e s u s m j e at e n e u k o at a n o m
v o r i u p o r e d m i n e r a l i z i r a j u e r e g i j e i z v j e z d a s t o g s u o b l i k a . V r e m e n s k e s t u d i j e
v o r i a u r a z v o j u u k a z u j u d a t e s t a n i c e n e n a s t a j u i z s t a n i c a s j a k o m p O B C o l 3 . 6 G F P c y a n a k t i v n o au , n i t i o n e p o s t a j u s t a n i c e s j a k i m c y a n i z r a ~a j e m . N i j e j a s n o d a l i t i j e k o m d i f e r e n c i j a c i j e o v e s t a n i c e p o s t a j u d i o m i n e r a l a . U t o m b i s l u
a j u p o p r i m i l e j a k G F P c y a n i z r a ~a j i i z g u b i l e z v j e z d a s t u m o r f o l o g i j u . P r e t p o s t a v k a j e d a s e u k o s t i t e s t a n i c e p r e z e n t i r a j u k a o s a m o h O C - G F P t p z + s t a n i c e , j e r s e s l a b i i z r a ~a j G F P c y a n b i l j e g a n e m o ~e v i d j e t i . O v e s t a n i c e n a l a z i m o n a e n d o s t e a l n o j p o v r ai n i d i j a f i z e i u v r a t u b e d r e n e k o s t i . I p a k , o n e b i t a k o e r m o g l e b i t i p r e d s t a v l j e n e O C p o z i t i v n i m s t a n i c a m a u m e t a f i z n o j r e g i j i p e r i o s t e u m a k o j a s e n a s t a v l j a n a z g l o b n u h r s k a v i c u . Z r e l i o s t e o c i t i n i s u o b i l j e ~e n i n i t i s j e d n i m b i l j e g g e n o m . U s p r k o s ai r o k o j u p o r a b i o s t e o k a l c i n a k a o b i l j e g a o s t e o b l a s t i
n e d i f e r e n c i j a c i j e u s t a n i
n i m k u l t u r a m a , b r o j s t a n i c a s O C i z r a ~a j e m u n u t a r u k u p n e s t a n i
n e p o p u l a c i j e j e o k o 5 % , at o o v i s i o j a
i n i m i n e r a l i z i r a n o s t i k u l t u r e . V e i n a g e n a p o v e z a n a s d i f e r e n c i r a n i m o s t e o b l a s t i m a n i j e s p e c i f i
n a z a o s t e o b l a s t e , t e e s e r e l a t i v n a v a ~n o s t o v i h z a j e d n i
k i h g e n a m o i o c i j e n i t i k a d a 5 % s t a n i c a k o j e s u d o s e g l e p u n u o s t e o b l a s t i
n u d i f e r e n c i j a c i j u b u d u i s p i t a n e k a o i z o l i r a n a p o p u l a c i j a . S l i
n o , s t a n i c e k o j e s e n a l a z e n a p o v r ai n i k o s t i n e m a j u i s t i G F P i z r a ~a j u p u u j u i n a r a z l i
i t e r a z i n e o s t e o b l a s t i
n e d i f e r e n c i j a c i j e .
2 . P R I M J E N A G F P T R A N S G E N I N I H M I `E V A U M O D E L U H E T E R O T O P I N O G O K O `T A V A N J A
2 . 1 . N o v a m e t o d a h e t e r o t o p i
n e k o at a n e f o r m a c i j e - t o t a l n o o z r a
e n j e t i j e l a ( T O T ) u z t r a n s p l a n t a c i j u k o m p l e t n e k o at a n e s r ~i ( K K S )
U p o r a b o m k o l a g e n s k o g g e l a i z o l i r a n o g i z t e t i v e at a k o r s k o g r e p a k a o n o s a
a s t r o m a l n i h s t a n i c a , t e G F P t r a n s g e n i
n i h m i ae v a k a o p r i m a t e l j a i d a v a t e l j a s t r o m a l n i h s t a n i c a i k o m p l e t n e k o at a n e s r ~i ( K K S ) r a z v i l i s m o n o v i m o d e l h e t e r o t o p i
n e k o at a n e f o r m a c i j e . I s t o v r e m e n o s i m p l a n t a c i j o m p r i m a t e l j i s u p o d v r g n u t i t o t a l n o m o z r a
e n j u t i j e l a ( T O T ) t e s p a aa v a n j u s K K S d a b i s e u m a n j i l a r e a k c i j a o d b a c i v a n j a h e t e r o t o p i
n o g i m p l a n t a t a A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > W a n g < / A u t h o r > < Y e a r > 2 0 0 5 < / Y e a r > < R e c N u m > 1 3 4 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 6 0 8 1 6 9 4 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 0 6 < / V O L U M E > < N U M B E R > 1 0 < / N U M B E R > < Y E A R > 2 0 0 5 < / Y E A R > < D A T E > N o v 1 5 < / D A T E > < T I T L E > H e t e r o g e n e i t y o f e n g r a f t e d b o n e - l i n i n g c e l l s a f t e r s y s t e m i c a n d l o c a l t r a n s p l a n t a t i o n < / T I T L E > < P A G E S > 3 6 5 0 - 7 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n , 0 6 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > W a n g , L . < / A U T H O R > < A U T H O R > L i u , Y . < / A U T H O R > < A U T H O R > K a l a j z i c , Z . < / A U T H O R > < A U T H O R > J i a n g , X . < / A U T H O R > < A U T H O R > R o w e , D . W . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B l o o d < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w T r a n s p l a n t a t i o n / m e t h o d s < / K E Y W O R D > < K E Y W O R D > C a l c i f i c a t i o n , P h y s i o l o g i c / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > E x t r a c e l l u l a r M a t r i x / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n R e g u l a t i o n / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > M o d e l s , A n i m a l < / K E Y W O R D > < K E Y W O R D > O r g a n S p e c i f i c i t y / p h y s i o l o g y / r a d i a t i o n e f f e c t s < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / c y t o l o g y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > O s t e o g e n e s i s / * p h y s i o l o g y / r a d i a t i o n e f f e c t s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N . I . H . , E x t r a m u r a l < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S k u l l / c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n C h i m e r a / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n , H o m o l o g o u s < / K E Y W O R D > < K E Y W O R D > W h o l e - B o d y I r r a d i a t i o n / m e t h o d s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 6 0 8 1 6 9 4 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 2 5 ) . I a k o o v a j k o r a k m o ~d a n i j e u
i n k o v i t k a o i z v o e n j e e k s p e r i m e n t a u i m u n k o m p r o m i t i r a n i m i s i n g e n i
n i m m i ae v i m a , o n n a m p r o ai r u j e m o g u n o s t i i z v o e n j a t r a n s p l a n t a c i j s k i h e k s p e r i m e n a t a t e s m a n j u j e n j i h o v e t r o ak o v e . M n o g i k n o c k o u t i t r a n s g e n i
n i m i ae v i k o j i n o s e m u t a c i j e o d i n t e r e s a n i s u u C 5 7 B l / 6 s i n g e n i
n i m m i ae v i m a , n i t i u i m u n o k o m p r i m i t i r a n i m ~i v o t i n j a m a . U p o r a b o m o v o g a p r o t o k o l a b i l i s m o u m o g u n o s t i m i j e aa t i C D 1 , C 5 7 B l / 6 i 1 2 9 g e n e t i
k u p o z a d i n u b e z z n a k o v a s t a n i
n o g i n f i l t r a t a k o j i s e r a z v i j a a k o p r e s k o
i m o T O T / K K S k o r a k . M o g u a j e p r i s u t n o s t o d b a c i v a n j a n i s k o g s t u p n j a , n o n j e z i n i n t e n z i t e t n i j e m j e r l j i v h i s t o l o ak i m m e t o d a m a . I a k o s e T O T / K K S k o r a k
i n i d o v o l j a n z a u s p j e an u i m p l a n t a c i j u m i aj i h s t a n i c a , i m p l a n t i r a n e h u m a n e s t a n i c e i z a z v a l e s u j a k u i m u n u r e a k c i j u k o j a j e z a u s t a v i l a k o at a n u f o r m a c i j u u i m u n o d e f i c i j e n t n o m m i au . O v a j p r o t o k o l i m a p r e d n o s t k o r i at e n j a p o p u l a c i j e G F P o b i l j e ~e n i h s t a n i c a d a b i s m o p r o c i j e n i l i d o p r i n o s k o at a n e s r ~i u s t v a r a n j u n o v e k o s t i .
2 . 2 . E n d o t e l n e s t a n i c e u p r o c e s u s t v a r a n j a n o v e k o s t i
O v a s t u d i j a o t k r i v a d o p r i n o s s t a n i c a k o at a n e s r ~i u s t v a r a n j u e n d o t e l n e m r e ~e k o j a p r e t h o d i s t v a r a n j u k o s t i . B M S C s u i z o l i r a n e i z T i e 2 e G F P i l i p O B C o l 3 . 6 G F P c y a n t r a n s g e n i
n i h m i ae v a , s t a v l j e n e u k o l a g e n s k i n o s a
i i m p l a n t i r a n e s u p k u t a n o u o z r a
e n e p O B C o l 3 . 6 G F P c y a n i l i T i e 2 e G F P p r i m a t e l j e i n j i c i r a n e s o d g o v a r a j u o m K K S ( T a b l i c a 1 , E k s p e r i m e n t 1 i 2 ) . O v e G F P k o m b i n a c i j e s u p o k a z a l e d a s v e C D 3 1 + e n d o t e l n e s t a n i c e u i m p l a n t a t u p o t j e
u o d d a v a t e l j a , a n e o d p r i m a t e l j a . P r i m a t e l j e v e e n d o t e l n e s t a n i c e s e n a l a z e u f i b r o z n o j k a p s u l i k o j a o k r u ~u j e i m p l a n t a t , t e j e v j e r o j a t n o d a s e o v d j e s p a j a j u d o m a i n o v e i d o n o r o v e e n d o t e l n e s t a n i c e . P o t e n c i j a l B M S C s t a n i c a d a d i f e r e n c i r a j u u e n d o t e l n e s t a n i c e p r i j e j e i s t r a ~e n a u M a t r i g e l m o d e l u A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > A l - K h a l d i < / A u t h o r > < Y e a r > 2 0 0 3 < / Y e a r > < R e c N u m > 3 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 2 6 9 2 5 9 0 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 0 < / V O L U M E > < N U M B E R > 8 < / N U M B E R > < Y E A R > 2 0 0 3 < / Y E A R > < D A T E > A p r < / D A T E > < T I T L E > P o s t n a t a l b o n e m a r r o w s t r o m a l c e l l s e l i c i t a p o t e n t V E G F - d e p e n d e n t n e o a n g i o g e n i c r e s p o n s e i n v i v o < / T I T L E > < P A G E S > 6 2 1 - 9 < / P A G E S > < A U T H O R _ A D D R E S S > M c G i l l U n i v e r s i t y H e a l t h C e n t e r , M o n t r e a l , Q u e b e c , C a n a d a . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > A l - K h a l d i , A . < / A U T H O R > < A U T H O R > E l i o p o u l o s , N . < / A U T H O R > < A U T H O R > M a r t i n e a u , D . < / A U T H O R > < A U T H O R > L e j e u n e , L . < / A U T H O R > < A U T H O R > L a c h a p e l l e , K . < / A U T H O R > < A U T H O R > G a l i p e a u , J . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > G e n e T h e r < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w T r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C o l l a g e n < / K E Y W O R D > < K E Y W O R D > C y t i d i n e D e a m i n a s e / g e n e t i c s < / K E Y W O R D > < K E Y W O R D > D r u g C o m b i n a t i o n s < / K E Y W O R D > < K E Y W O R D > E n d o t h e l i a l G r o w t h F a c t o r s / i m m u n o l o g y / * p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > E n d o t h e l i u m , V a s c u l a r / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t G r o w t h F a c t o r 2 / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > G r e e n F l u o r e s c e n t P r o t e i n s < / K E Y W O R D > < K E Y W O R D > I m m u n e S e r a / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > I n t e r c e l l u l a r S i g n a l i n g P e p t i d e s a n d P r o t e i n s / i m m u n o l o g y / * p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > L a c O p e r o n < / K E Y W O R D > < K E Y W O R D > L a m i n i n < / K E Y W O R D > < K E Y W O R D > L u m i n e s c e n t P r o t e i n s / g e n e t i c s < / K E Y W O R D > < K E Y W O R D > L y m p h o k i n e s / i m m u n o l o g y / * p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C 5 7 B L < / K E Y W O R D > < K E Y W O R D > M o d e l s , A n i m a l < / K E Y W O R D > < K E Y W O R D > * N e o v a s c u l a r i z a t i o n , P h y s i o l o g i c < / K E Y W O R D > < K E Y W O R D > P r o t e o g l y c a n s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > T r a n s d u c t i o n , G e n e t i c < / K E Y W O R D > < K E Y W O R D > V a s c u l a r E n d o t h e l i a l G r o w t h F a c t o r A < / K E Y W O R D > < K E Y W O R D > V a s c u l a r E n d o t h e l i a l G r o w t h F a c t o r s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 2 6 9 2 5 9 0 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > A n n a b i < / A u t h o r > < Y e a r > 2 0 0 4 < / Y e a r > < R e c N u m > 5 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 0 4 8 8 7 0 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 9 1 < / V O L U M E > < N U M B E R > 6 < / N U M B E R > < Y E A R > 2 0 0 4 < / Y E A R > < D A T E > A p r 1 5 < / D A T E > < T I T L E > V a s c u l a r p r o g e n i t o r s d e r i v e d f r o m m u r i n e b o n e m a r r o w s t r o m a l c e l l s a r e r e g u l a t e d b y f i b r o b l a s t g r o w t h f a c t o r a n d a r e a v i d l y r e c r u i t e d b y v a s c u l a r i z i n g t u m o r s < / T I T L E > < P A G E S > 1 1 4 6 - 5 8 < / P A G E S > < A U T H O R _ A D D R E S S > L a b o r a t o i r e d & a p o s ; O n c o l o g i e M o l e c u l a i r e , D e p a r t m e n t o f B i o c h e m i s t r y , U n i v e r s i t e d u Q u e b e c a M o n t r e a l , C . P . 8 8 8 8 , S u c c . C e n t r e - v i l l e , M o n t r e a l , Q u e b e c , C a n a d a H 3 C 3 P 8 . a n n a b i . b o r h a n e @ u q a m . c a < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > A n n a b i , B . < / A U T H O R > < A U T H O R > N a u d , E . < / A U T H O R > < A U T H O R > L e e , Y . T . < / A U T H O R > < A U T H O R > E l i o p o u l o s , N . < / A U T H O R > < A U T H O R > G a l i p e a u , J . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J C e l l B i o c h e m < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > A n t i g e n s , C D 3 1 / i m m u n o l o g y < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s / * c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C a t t l e < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n / i m m u n o l o g y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l L i n e , T u m o r < / K E Y W O R D > < K E Y W O R D > C o c u l t u r e T e c h n i q u e s / m e t h o d s < / K E Y W O R D > < K E Y W O R D > C r i c e t i n a e < / K E Y W O R D > < K E Y W O R D > E n d o t h e l i a l C e l l s / c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t G r o w t h F a c t o r 2 / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , N u d e < / K E Y W O R D > < K E Y W O R D > N e o p l a s m s / * b l o o d s u p p l y < / K E Y W O R D > < K E Y W O R D > N e o v a s c u l a r i z a t i o n , P a t h o l o g i c / * p a t h o l o g y / p h y s i o p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > P a r a c r i n e C o m m u n i c a t i o n < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > S t e m C e l l s / * c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / c y t o l o g y / i m m u n o l o g y / p h y s i o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 0 4 8 8 7 0 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 5 , 8 3 ) . U t i m s t u d i j a m a s a m o 1 - 5 % k r v n i h ~i l a u i m p l a n t a t u j e b i l a d o n o r s k o g p o d r i j e t l a . O v o n e s l a g a n j e s r e z u l t a t i m a n a ae g r a d a v j e r o j a t n o p r o i s t j e
e z b o g e n d o t e l n i h f a k t o r a p r i s u t n i h u m e m b r a n i M a t r i g e l a k o j i p o t i
u s n a ~n u r e a k c i j u v a s k u l a r i z a c i j e o d s t r a n e d o m a i n a . N e s a m o d a d o m a i n n i j e p r i d o n i o l o k a l n o m r a s t u e n d o t e l n i h s t a n i c a , n e g o n i j e b i l o n i d o k a z a d a s u e n d o t e l n e s t a n i c e k o at a n e s r ~i p r i s u t n e u n u t a r h e t e r o t o p i
n e k o s t i p o t e k l e o d d o m a i n a . D a k l e , u o v o m m o d e l u v a s k u l a r i z a c i j e d o m a i n o v e e n d o t e l n e s t a n i c e n i s u p r i d o n i j e l e n i t i u r a s t a n j e m n i t i p u t e m c i r k u l a c i j e . D r u g i
i m b e n i k k o j i m o ~e u t j e c a t i n a r a z v o j k r v n i h ~i l a j e F G F 2 k o j i p r o m o v i r a d i f e r e n c i j a c i j u v a s k u l a r n i h p r o g e n i t o r s k i h s t a n i c a u n u t a r s t a n i
n e p o p u l a c i j e k o at a n e s r ~i A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > A l l o u c h e < / A u t h o r > < Y e a r > 1 9 9 5 < / Y e a r > < R e c N u m > 6 1 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 7 5 9 6 1 8 0 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 9 < / V O L U M E > < N U M B E R > 6 < / N U M B E R > < Y E A R > 1 9 9 5 < / Y E A R > < D A T E > J u n < / D A T E > < T I T L E > B a s i c f i b r o b l a s t g r o w t h f a c t o r a n d h e m a t o p o i e s i s < / T I T L E > < P A G E S > 9 3 7 - 4 2 < / P A G E S > < A U T H O R _ A D D R E S S > L a b o r a t o i r e C N R S , C e n t r e C l a u d i u s R e g a u d , T o u l o u s e , F r a n c e . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > A l l o u c h e , M . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > L e u k e m i a < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > C e l l L i n e < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t G r o w t h F a c t o r 2 / b i o s y n t h e s i s / p h a r m a c o l o g y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e s i s / d r u g e f f e c t s / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / * c y t o l o g y / d r u g e f f e c t s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H o m e o s t a s i s < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > L e u k e m i a / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > M e s o d e r m / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > M o d e l s , B i o l o g i c a l < / K E Y W O R D > < K E Y W O R D > R e c e p t o r s , F i b r o b l a s t G r o w t h F a c t o r / b i o s y n t h e s i s < / K E Y W O R D > < K E Y W O R D > T r a n s f o r m i n g G r o w t h F a c t o r b e t a / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > T u m o r C e l l s , C u l t u r e d < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 7 5 9 6 1 8 0 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 2 6 ) , n o b e z u t j e c a j a n a n j i h o v o s t e o g e n i p o t e n c i j a l A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > B i a n c h i < / A u t h o r > < Y e a r > 2 0 0 3 < / Y e a r > < R e c N u m > 6 2 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 2 7 9 9 1 8 6 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 8 7 < / V O L U M E > < N U M B E R > 1 < / N U M B E R > < Y E A R > 2 0 0 3 < / Y E A R > < D A T E > J u l 1 < / D A T E > < T I T L E > E x v i v o e n r i c h m e n t o f m e s e n c h y m a l c e l l p r o g e n i t o r s b y f i b r o b l a s t g r o w t h f a c t o r 2 < / T I T L E > < P A G E S > 9 8 - 1 0 5 < / P A G E S > < A U T H O R _ A D D R E S S > I s t i t u t o N a z i o n a l e p e r l a R i c e r c a s u l C a n c r o , G e n o v a , I t a l y . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > B i a n c h i , G . < / A U T H O R > < A U T H O R > B a n f i , A . < / A U T H O R > < A U T H O R > M a s t r o g i a c o m o , M . < / A U T H O R > < A U T H O R > N o t a r o , R . < / A U T H O R > < A U T H O R > L u z z a t t o , L . < / A U T H O R > < A U T H O R > C a n c e d d a , R . < / A U T H O R > < A U T H O R > Q u a r t o , R . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > E x p C e l l R e s < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A d o l e s c e n t < / K E Y W O R D > < K E Y W O R D > A d u l t < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s / * d r u g e f f e c t s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w T r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l C o u n t < / K E Y W O R D > < K E Y W O R D > C e l l C u l t u r e T e c h n i q u e s / * m e t h o d s < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n / d r u g e f f e c t s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n / d r u g e f f e c t s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l S u r v i v a l / d r u g e f f e c t s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C l o n e C e l l s / d r u g e f f e c t s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > C o l o n y - F o r m i n g U n i t s A s s a y < / K E Y W O R D > < K E Y W O R D > D N A - B i n d i n g P r o t e i n s < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t G r o w t h F a c t o r 2 / * p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l T r a n s p l a n t a t i o n / * m e t h o d s < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / c y t o l o g y / * d r u g e f f e c t s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M e s o d e r m / c y t o l o g y / * d r u g e f f e c t s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > M i d d l e A g e d < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / * d r u g e f f e c t s / m e t a b o l i s m / t r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > T e l o m e r a s e / d r u g e f f e c t s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > T e l o m e r e / d r u g e f f e c t s / p h y s i o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 2 7 9 9 1 8 6 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > K a l a j z i c < / A u t h o r > < Y e a r > 2 0 0 3 < / Y e a r > < R e c N u m > 2 7 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 2 6 4 7 2 9 9 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 8 8 < / V O L U M E > < N U M B E R > 6 < / N U M B E R > < Y E A R > 2 0 0 3 < / Y E A R > < D A T E > A p r 1 5 < / D A T E > < T I T L E > S t a g e s p e c i f i c i n h i b i t i o n o f o s t e o b l a s t l i n e a g e d i f f e r e n t i a t i o n b y F G F 2 a n d n o g g i n < / T I T L E > < P A G E S > 1 1 6 8 - 7 6 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n , C o n n e c t i c u t 0 6 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > K a l a j z i c , I . < / A U T H O R > < A U T H O R > K a l a j z i c , Z . < / A U T H O R > < A U T H O R > H u r l e y , M . M . < / A U T H O R > < A U T H O R > L i c h t l e r , A . C . < / A U T H O R > < A U T H O R > R o w e , D . W . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J C e l l B i o c h e m < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > C a r r i e r P r o t e i n s < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n / d r u g e f f e c t s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t G r o w t h F a c t o r 2 / g e n e t i c s / * p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > G e n e T h e r a p y < / K E Y W O R D > < K E Y W O R D > G r e e n F l u o r e s c e n t P r o t e i n s < / K E Y W O R D > < K E Y W O R D > G r o w t h I n h i b i t o r s / * p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > L u m i n e s c e n t P r o t e i n s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / d r u g e f f e c t s / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > P r o t e i n s / a n t a g o n i s t s & a m p ; i n h i b i t o r s / g e n e t i c s / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S t e m C e l l s / d r u g e f f e c t s / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s g e n e s / d r u g e f f e c t s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 2 6 4 7 2 9 9 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > M a r t i n < / A u t h o r > < Y e a r > 1 9 9 7 < / Y e a r > < R e c N u m > 7 4 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 9 3 2 2 9 6 3 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 3 8 < / V O L U M E > < N U M B E R > 1 0 < / N U M B E R > < Y E A R > 1 9 9 7 < / Y E A R > < D A T E > O c t < / D A T E > < T I T L E > F i b r o b l a s t g r o w t h f a c t o r - 2 s u p p o r t s e x v i v o e x p a n s i o n a n d m a i n t e n a n c e o f o s t e o g e n i c p r e c u r s o r s f r o m h u m a n b o n e m a r r o w < / T I T L E > < P A G E S > 4 4 5 6 - 6 2 < / P A G E S > < A U T H O R _ A D D R E S S > L a b o r a t o r i o d i D i f f e r e n z i a m e n t o C e l l u l a r e , I s t i t u t o N a z i o n a l e p e r l a R i c e r c a s u l C a n c r o / C e n t r o d i B i o t e c n o l o g i e A v a n z a t e , G e n o v a , I t a l y . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > M a r t i n , I . < / A U T H O R > < A U T H O R > M u r a g l i a , A . < / A U T H O R > < A U T H O R > C a m p a n i l e , G . < / A U T H O R > < A U T H O R > C a n c e d d a , R . < / A U T H O R > < A U T H O R > Q u a r t o , R . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > E n d o c r i n o l o g y < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A d u l t < / K E Y W O R D > < K E Y W O R D > A l k a l i n e P h o s p h a t a s e / a n a l y s i s < / K E Y W O R D > < K E Y W O R D > A s c o r b i c A c i d / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w / d r u g e f f e c t s / e n z y m o l o g y < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w C e l l s < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n / d r u g e f f e c t s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C h i l d < / K E Y W O R D > < K E Y W O R D > D e x a m e t h a s o n e / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > E p i d e r m a l G r o w t h F a c t o r / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t G r o w t h F a c t o r 2 / * p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t s / c y t o l o g y / d r u g e f f e c t s / e n z y m o l o g y < / K E Y W O R D > < K E Y W O R D > G l y c e r o p h o s p h a t e s / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > G r o w t h H o r m o n e / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > G r o w t h S u b s t a n c e s / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > I n s u l i n - L i k e G r o w t h F a c t o r I / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > P l a t e l e t - D e r i v e d G r o w t h F a c t o r / p h a r m a c o l o g y < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > S t e m C e l l s / * c y t o l o g y / d r u g e f f e c t s / e n z y m o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s f o r m i n g G r o w t h F a c t o r b e t a / p h a r m a c o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 9 3 2 2 9 6 3 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > Z h a n g < / A u t h o r > < Y e a r > 2 0 0 2 < / Y e a r > < R e c N u m > 7 9 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 1 7 7 9 2 0 3 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 9 0 < / V O L U M E > < N U M B E R > 1 < / N U M B E R > < Y E A R > 2 0 0 2 < / Y E A R > < D A T E > J a n 1 1 < / D A T E > < T I T L E > F G F - 2 i n c r e a s e s c o l o n y f o r m a t i o n , P T H r e c e p t o r , a n d I G F - 1 m R N A i n m o u s e m a r r o w s t r o m a l c e l l s < / T I T L E > < P A G E S > 5 2 6 - 3 1 < / P A G E S > < A U T H O R _ A D D R E S S > U n i v e r s i t y o f C o n n e c t i c u t S c h o o l o f M e d i c i n e , F a r m i n g t o n , C T 0 6 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > Z h a n g , X . < / A U T H O R > < A U T H O R > S o b u e , T . < / A U T H O R > < A U T H O R > H u r l e y , M . M . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B i o c h e m B i o p h y s R e s C o m m u n < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s / * m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > B o n e a n d B o n e s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C o l l a g e n T y p e I / b i o s y n t h e s i s < / K E Y W O R D > < K E Y W O R D > D N A , C o m p l e m e n t a r y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > D o s e - R e s p o n s e R e l a t i o n s h i p , D r u g < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t G r o w t h F a c t o r 2 / * m e t a b o l i s m / p h a r m a c o l o g y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > I n s u l i n - L i k e G r o w t h F a c t o r I / * b i o s y n t h e s i s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C 5 7 B L < / K E Y W O R D > < K E Y W O R D > * N e o p l a s m P r o t e i n s < / K E Y W O R D > < K E Y W O R D > O s t e o c a l c i n / b i o s y n t h e s i s < / K E Y W O R D > < K E Y W O R D > P a r a t h y r o i d H o r m o n e / b i o s y n t h e s i s < / K E Y W O R D > < K E Y W O R D > R N A , M e s s e n g e r / * m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R a t s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / * m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > T i m e F a c t o r s < / K E Y W O R D > < K E Y W O R D > T r a n s c r i p t i o n F a c t o r s / m e t a b o l i s m < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 1 7 7 9 2 0 3 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 8 9 - 9 1 , 1 2 7 ) . N e d a v n a i s t r a ~i v a n j a u k a z u j u d a h e m a t o p o e t s k e s t a n i c e i o s t e o b l a s t i n a s t a j u i z z a j e d n i
k e p r o g e n i t o r s k e s t a n i c e n a k o n t r a n s p l a n t a c i j e k o at a n e s r ~i A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > D o m i n i c i < / A u t h o r > < Y e a r > 2 0 0 4 < / Y e a r > < R e c N u m > 6 5 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 2 8 2 3 7 7 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 0 1 < / V O L U M E > < N U M B E R > 3 2 < / N U M B E R > < Y E A R > 2 0 0 4 < / Y E A R > < D A T E > A u g 1 0 < / D A T E > < T I T L E > H e m a t o p o i e t i c c e l l s a n d o s t e o b l a s t s a r e d e r i v e d f r o m a c o m m o n m a r r o w p r o g e n i t o r a f t e r b o n e m a r r o w t r a n s p l a n t a t i o n < / T I T L E > < P A G E S > 1 1 7 6 1 - 6 < / P A G E S > < A U T H O R _ A D D R E S S > D i v i s i o n o f E x p e r i m e n t a l H e m a t o l o g y , S t . J u d e C h i l d r e n & a p o s ; s R e s e a r c h H o s p i t a l , 3 3 2 N o r t h L a u d e r d a l e S t r e e t , M e m p h i s , T N 3 8 1 0 5 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > D o m i n i c i , M . < / A U T H O R > < A U T H O R > P r i t c h a r d , C . < / A U T H O R > < A U T H O R > G a r l i t s , J . E . < / A U T H O R > < A U T H O R > H o f m a n n , T . J . < / A U T H O R > < A U T H O R > P e r s o n s , D . A . < / A U T H O R > < A U T H O R > H o r w i t z , E . M . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > P r o c N a t l A c a d S c i U S A < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B l o o d C e l l s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w T r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > B o n e a n d B o n e s / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > * C e l l L i n e a g e < / K E Y W O R D > < K E Y W O R D > C l o n e C e l l s < / K E Y W O R D > < K E Y W O R D > G r a f t S u r v i v a l < / K E Y W O R D > < K E Y W O R D > K a r y o t y p i n g < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d S t r a i n s < / K E Y W O R D > < K E Y W O R D > M u l t i p o t e n t S t e m C e l l s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > O s t e o c y t e s / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 2 8 2 3 7 7 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 2 8 ) , at o u p u u j e n a m o g u n o s t p o s t o j a n j a j e d n e z a j e d n i
k e p r o g e n i t o r s k e s t a n i c e , h e m a n g i o b l a s t a A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > C h o i < / A u t h o r > < Y e a r > 2 0 0 2 < / Y e a r > < R e c N u m > 1 5 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 1 8 4 7 0 0 6 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 1 < / V O L U M E > < N U M B E R > 1 < / N U M B E R > < Y E A R > 2 0 0 2 < / Y E A R > < D A T E > F e b < / D A T E > < T I T L E > T h e h e m a n g i o b l a s t : a c o m m o n p r o g e n i t o r o f h e m a t o p o i e t i c a n d e n d o t h e l i a l c e l l s < / T I T L E > < P A G E S > 9 1 - 1 0 1 < / P A G E S > < A U T H O R _ A D D R E S S > S c h o o l o f M e d i c i n e , D e p a r t m e n t o f P a t h o l o g y a n d I m m u n o l o g y , W a s h i n g t o n U n i v e r s i t y , 6 6 0 S o u t h E u c l i d A v e n u e , S t . L o u i s , M O 6 3 1 1 0 , U S A . k c h o i @ i m m u n o l o g y . w u s t l . e d u < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > C h o i , K . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > J H e m a t o t h e r S t e m C e l l R e s < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l L i n e a g e < / K E Y W O R D > < K E Y W O R D > E n d o t h e l i u m , V a s c u l a r / c y t o l o g y / e m b r y o l o g y < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > N e o v a s c u l a r i z a t i o n , P h y s i o l o g i c / d r u g e f f e c t s < / K E Y W O R D > < K E Y W O R D > S t e m C e l l s / * c y t o l o g y / d r u g e f f e c t s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 1 8 4 7 0 0 6 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 7 1 ) , z a e n d o t e l n e s t a n i c e , s t a n i c e k o at a n e s r ~i i o s t e o b l a s t e .
2 . 3 . D o p r i n o s d a v a t e l j a v s . p r i m a t e l j a p r i l i k o m s t v a r a n j a h e t e r o t o p i
n e k o s t i
D o k j e p o t e n c i j a l d o n o r s k i h s t r o m a l n i h s t a n i c a u n o v o j k o at a n o j f o r m a c i j i d o b r o p o z n a t , r e l a t i v n i d o p r i n o s d o m a i n a m o ~e b i t i v r l o v a r i j a b i l a n A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > F r i e d e n s t e i n < / A u t h o r > < Y e a r > 1 9 7 1 < / Y e a r > < R e c N u m > 6 6 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 4 9 3 6 7 5 6 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 2 < / V O L U M E > < N U M B E R > 2 < / N U M B E R > < Y E A R > 1 9 7 1 < / Y E A R > < D A T E > A u g < / D A T E > < T I T L E > O s t e o g e n i c p r e c u r s o r c e l l s o f b o n e m a r r o w i n r a d i a t i o n c h i m e r a s < / T I T L E > < P A G E S > 9 9 - 1 0 8 < / P A G E S > < A U T H O R S > < A U T H O R > F r i e d e n s t e i n , A . < / A U T H O R > < A U T H O R > K u r a l e s o v a , A . I . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > T r a n s p l a n t a t i o n < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w C e l l s < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w T r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > G r a f t R e j e c t i o n < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s < / K E Y W O R D > < K E Y W O R D > H i s t o c o m p a t i b i l i t y < / K E Y W O R D > < K E Y W O R D > K i d n e y / s u r g e r y < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > M e t h o d s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > * O s t e o g e n e s i s < / K E Y W O R D > < K E Y W O R D > * R a d i a t i o n C h i m e r a < / K E Y W O R D > < K E Y W O R D > R a d i a t i o n I n j u r i e s , E x p e r i m e n t a l < / K E Y W O R D > < K E Y W O R D > * T r a n s p l a n t a t i o n I m m u n o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n , H o m o l o g o u s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 4 9 3 6 7 5 6 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > F r i e d e n s t e i n < / A u t h o r > < Y e a r > 1 9 7 8 < / Y e a r > < R e c N u m > 6 7 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 3 5 0 5 9 6 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 6 < / V O L U M E > < N U M B E R > 5 < / N U M B E R > < Y E A R > 1 9 7 8 < / Y E A R > < D A T E > M a y < / D A T E > < T I T L E > O r i g i n o f b o n e m a r r o w s t r o m a l m e c h a n o c y t e s i n r a d i o c h i m e r a s a n d h e t e r o t o p i c t r a n s p l a n t s < / T I T L E > < P A G E S > 4 4 0 - 4 < / P A G E S > < A U T H O R S > < A U T H O R > F r i e d e n s t e i n , A . J . < / A U T H O R > < A U T H O R > I v a n o v - S m o l e n s k i , A . A . < / A U T H O R > < A U T H O R > C h a j l a k j a n , R . K . < / A U T H O R > < A U T H O R > G o r s k a y a , U . F . < / A U T H O R > < A U T H O R > K u r a l e s o v a , A . I . < / A U T H O R > < A U T H O R > L a t z i n i k , N . W . < / A U T H O R > < A U T H O R > G e r a s i m o w , U . W . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > E x p H e m a t o l < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w / i m m u n o l o g y < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w T r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C y t o t o x i c i t y , I m m u n o l o g i c < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t s / c y t o l o g y / i m m u n o l o g y / u l t r a s t r u c t u r e < / K E Y W O R D > < K E Y W O R D > F l u o r e s c e n t A n t i b o d y T e c h n i q u e < / K E Y W O R D > < K E Y W O R D > G u i n e a P i g s < / K E Y W O R D > < K E Y W O R D > H i s t o c o m p a t i b i l i t y A n t i g e n s < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C 5 7 B L < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C B A < / K E Y W O R D > < K E Y W O R D > * R a d i a t i o n C h i m e r a < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n , H e t e r o l o g o u s < / K E Y W O R D > < K E Y W O R D > X C h r o m o s o m e < / K E Y W O R D > < K E Y W O R D > Y C h r o m o s o m e < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 3 5 0 5 9 6 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > F r i e d e n s t e i n < / A u t h o r > < Y e a r > 1 9 6 8 < / Y e a r > < R e c N u m > 6 8 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 5 6 5 4 0 8 8 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 6 < / V O L U M E > < N U M B E R > 2 < / N U M B E R > < Y E A R > 1 9 6 8 < / Y E A R > < D A T E > M a r < / D A T E > < T I T L E > H e t e r o t o p i c o f b o n e m a r r o w . A n a l y s i s o f p r e c u r s o r c e l l s f o r o s t e o g e n i c a n d h e m a t o p o i e t i c t i s s u e s < / T I T L E > < P A G E S > 2 3 0 - 4 7 < / P A G E S > < A U T H O R S > < A U T H O R > F r i e d e n s t e i n , A . J . < / A U T H O R > < A U T H O R > P e t r a k o v a , K . V . < / A U T H O R > < A U T H O R > K u r o l e s o v a , A . I . < / A U T H O R > < A U T H O R > F r o l o v a , G . P . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > T r a n s p l a n t a t i o n < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > * H e m a t o p o i e s i s < / K E Y W O R D > < K E Y W O R D > K a r y o t y p i n g < / K E Y W O R D > < K E Y W O R D > K i d n e y < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > * O s t e o b l a s t s < / K E Y W O R D > < K E Y W O R D > * O s t e o g e n e s i s < / K E Y W O R D > < K E Y W O R D > * T r a n s p l a n t a t i o n I m m u n o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n , H o m o l o g o u s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 5 6 5 4 0 8 8 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > H o t t a < / A u t h o r > < Y e a r > 1 9 8 3 < / Y e a r > < R e c N u m > 7 0 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 6 8 3 2 2 4 0 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 1 < / V O L U M E > < N U M B E R > 2 < / N U M B E R > < Y E A R > 1 9 8 3 < / Y E A R > < D A T E > F e b < / D A T E > < T I T L E > O r i g i n s o f h e m o p o i e t i c a n d s t r o m a l c e l l s i n s u b c u t a n e o u s f e m u r i m p l a n t s < / T I T L E > < P A G E S > 1 0 7 - 1 3 < / P A G E S > < A U T H O R S > < A U T H O R > H o t t a , T . < / A U T H O R > < A U T H O R > M u r a t e , T . < / A U T H O R > < A U T H O R > U t s u m i , M . < / A U T H O R > < A U T H O R > H i r a b a y a s h i , N . < / A U T H O R > < A U T H O R > Y a m a d a , H . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > E x p H e m a t o l < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w C e l l s < / K E Y W O R D > < K E Y W O R D > * C h o r i s t o m a < / K E Y W O R D > < K E Y W O R D > C o l o n y - F o r m i n g U n i t s A s s a y < / K E Y W O R D > < K E Y W O R D > F e m u r / * t r a n s p l a n t a t i o n < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t s / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > K a r y o t y p i n g < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C 5 7 B L < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C B A < / K E Y W O R D > < K E Y W O R D > S p l e e n / c y t o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 6 8 3 2 2 4 0 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 1 5 , 1 2 9 - 1 3 1 ) . U o v o j s t u d i j i p O B C o l 3 . 6 G F P c y a n B M S C s u s e r a z v i l e , d v a t j e d n a n a k o n i m p l a n t a c i j e , k a o ai r o k o r a s p r ae n i G F P c y a n + f i b r o b l a s t i n i s k o g i n t e n z i t e t a . D o 3 . i 4 . t j e d n a m n o g e s u o d o v i h s t a n i c a p o s t a l e s n a ~n o G F P c y a n + t e s u s e s m j e s t i l e n a p o v r ai n i n o v o s t v o r e n e k o s t i i u k o at a n o m m a t r i k s u ( T a b l i c a 1 , E k s p e r i m e n t 2 ; S l i k a 2 1 ) . D o p r i n o s p r i m a t e l j e v i h k o at a n i h p r o g e n i t o r s k i h s t a n i c a p r o c i j e n j e n j e e k s p e r i m e n t o m s p O B C o l 3 . 6 G F P t p z t r a n s g e n i
n i m m i ae v i m a k a o d o m a i n i m a . G F P t p z p o z i t i v n e s t a n i c e d o b r o s u b i l e r a z v i j e n e u f i b r o z n o j k a p s u l i o k o i m p l a n t a t a , t e j e n e k o l i k o s t a n i c a p o k r a j i m p l a n t a t a i m a l o j a k i n t e n z i t e t G F P s i g n a l a k a r a k t e r i s t i
a n z a r a z v i j e n i o s t e o b l a s t ( T a b l i c a 1 , E k s p e r i m e n t 5 ; S l i k a 2 3 c i d ) . M o g u e b i o b j a an j e n j e b i l o d a s u o v e s t a n i c e n a s t a l e k a o o d g o v o r n a
i m b e n i k e k o at a n o g r a s t a k o j i p r o i z l a z e i z i m p l a n t a t a . D a k l e , k o at a n a f o r m a c i j a j e a p s o l u t n o o v i s n a o d o n o r s k i m p r o g e n i t o r s k i m s t a n i c a m a j e r n i t i j e d a n o s t e o b l a s t p o d r i j e t l o m i z d o m a i n a n i j e o p a ~e n u h e t e r o t o p i
n o j k o s t i b i l o d i r e k t n o m i n v a z i j o m i l i p u t e m c i r k u l a c i j e .
2 . 4 . P r i r o d a o b l o ~n i h s t a n i c a u k o at a n o j s r ~i h e t e r o t o p i
n e k o s t i
N e o
e k i v a n a j e b i l a p r i s u t n o s t s t a n i c a s m j e at e n i h n a p o v r ai n i n o v o s t v o r e n i h p r o s t o r a s k o at a n o m s r ~i u i m p l a n t a t u , k o j e s u p o t e k l e o d d o m a i n a i l i t r a n s p l a n t i r a n e K K S ( T a b l i c a 1 , E k s p e r i m e n t 1 ) t e s u v j e r o j a t n o s t i g l e p u t e m c i r k u l a c i j e . I a k o s u t e s t a n i c e b i l e o b i l j e ~e n e p O B C o l 3 . 6 G F P c y a n t r a n s g e n o m , o n e s u s e r a z l i k o v a l e o d p o p u l a c i j e s t a n i c a k o j e s t v a r a j u k o s t . P o j a v i l e s u s e u 3 . i 4 . t j e d n u s a m o u n u t a r k o at a n e s r ~i t e n i s u p r o al e f i b r o b l a s t i
n u f a z u u 2 . t j e d n u ( S l i k a 2 0 ) . O v e s t a n i c e n i k a d n i s u o p a ~e n e u k o at a n o m m a t r i k s u , t e s u s e p o j a v l j i v a l e n a p o v r ai n i e n d o s t e a l n e k o s t i n a m j e s t i m a i n v a z i j e k o at a n e s r ~i .
D a b i s m o o t k r i l i i z v o r o v i h s t a n i c a , n a p r a v l j e n a j e s e r i j a e k s p e r i m e n a t a s p O B C o l 3 . 6 G F P c y a n i l i t o p a z p o z i t i v n i m i l i n e t r a n s g e n i
n i m m i ae v i m a u r a z l i
i t i m k o m b i n a c i j a m a p r i m a t e l j a , t e B M S C i K K S d a v a t e l j a . K a d a s u G F P t p z s t r o m a l n e s t a n i c e i m p l a n t i r a n e u G F P c y a n d o m a i n a s p a ae n o g s n e t r a n s g e n i
n o m k o at a n o m s r ~i , G F P t p z s t a n i c e s u b i l e p r i s u t n e u n u t a r k o s t i , d o k s u G F P c y a n s t a n i c e b i l e n a p o v r ai n i k o s t i ( T a b l i c a 1 , E k s p e r i m e n t 4 ; S l i k a 2 3 a i b ) . I m p l a n t a c i j a n e t r a n s g e n i
n i h s t r o m a l n i h s t a n i c a u p O B C o l 3 . 6 G F P t p z d o m a i n a s p a ae n o g s p O B C o l 3 . 6 G F P c y a n K K S p o k a z a l a j e p r i s u s t v o c y a n i t o p a z p o z i t v n i h s t a n i c a p o v r ai n i k o s t i o k o h e m a t o p o e t s k o g t k i v a s n e k o l i k o z e l e n i h s t a n i c a u k o at a n o j s r ~i ( T a b l i c a 1 , E k s p e r i m e n t 3 ; S l i k a 2 2 ) . O v i m e k s p e r i m e n t i m a d o k a z a n o j e p o d r i j e t l o o b l o ~n i h s t a n i c a i z d o m a i n a i l i K K S s t a n i c a .
P r i r o d a e n d o s t e a l n i h o b l o ~n i h s t a n i c a j o a n i j e u t v r e n a . O n e m o g u p r e d s t a v l j a t i p o p u l a c i j u c i r k u l i r a j u i h f i b r o c i t a p o t e k l i h i z k o at a n e s r ~i A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > Q u a n < / A u t h o r > < Y e a r > 2 0 0 4 < / Y e a r > < R e c N u m > 7 5 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 0 1 0 3 2 6 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 3 6 < / V O L U M E > < N U M B E R > 4 < / N U M B E R > < Y E A R > 2 0 0 4 < / Y E A R > < D A T E > A p r < / D A T E > < T I T L E > C i r c u l a t i n g f i b r o c y t e s : c o l l a g e n - s e c r e t i n g c e l l s o f t h e p e r i p h e r a l b l o o d < / T I T L E > < P A G E S > 5 9 8 - 6 0 6 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f M e d i c i n e a n d D e r m a t o l o g y , S e c t i o n o f R h e u m a t o l o g y , Y a l e U n i v e r s i t y S c h o o l o f M e d i c i n e , P . O . B o x 2 0 8 0 3 1 , 3 0 0 C e d a r S t r e e t , T A C S 5 2 5 , N e w H a v e n , C T 0 6 5 2 0 - 8 0 3 1 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > Q u a n , T . E . < / A U T H O R > < A U T H O R > C o w p e r , S . < / A U T H O R > < A U T H O R > W u , S . P . < / A U T H O R > < A U T H O R > B o c k e n s t e d t , L . K . < / A U T H O R > < A U T H O R > B u c a l a , R . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > I n t J B i o c h e m C e l l B i o l < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A s t h m a / p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > B i o l o g i c a l M a r k e r s / a n a l y s i s < / K E Y W O R D > < K E Y W O R D > C o l l a g e n / * s e c r e t i o n < / K E Y W O R D > < K E Y W O R D > C o n n e c t i v e T i s s u e D i s e a s e s / p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t s / s e c r e t i o n < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > L e u k o c y t e s / c y t o l o g y / * p h y s i o l o g y / s e c r e t i o n < / K E Y W O R D > < K E Y W O R D > N e o p l a s m s / m e t a b o l i s m / p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > P r o t e i n s / s e c r e t i o n < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > W o u n d H e a l i n g < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 0 1 0 3 2 6 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 3 2 ) . B u d u i d a o v a j t i p s t a n i c a i m a u l o g u p r i c i j e l j e n j u r a n a , m o g a o b i m a n i f e s t i r a t i k a s n o o d b a c i v a n j e i m p l a n t a t a r a d i o p o r a v k a i m u n o g s u s t a v a d o m a i n a . S u k l a d n o n a ae m r a d u ,
i n i s e d a f i b r o c i t i n a s t a j u i z d i j e l a k o at a n e s r ~i o t p o r n o g n a z r a
e n j e A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > B u c a l a < / A u t h o r > < Y e a r > 1 9 9 4 < / Y e a r > < R e c N u m > 6 3 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 8 7 9 0 6 0 3 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 < / V O L U M E > < N U M B E R > 1 < / N U M B E R > < Y E A R > 1 9 9 4 < / Y E A R > < D A T E > N o v < / D A T E > < T I T L E > C i r c u l a t i n g f i b r o c y t e s d e f i n e a n e w l e u k o c y t e s u b p o p u l a t i o n t h a t m e d i a t e s t i s s u e r e p a i r < / T I T L E > < P A G E S > 7 1 - 8 1 < / P A G E S > < A U T H O R _ A D D R E S S > P i c o w e r I n s t i t u t e f o r M e d i c a l R e s e a r c h , M a n h a s s e t , N e w Y o r k 1 1 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > B u c a l a , R . < / A U T H O R > < A U T H O R > S p i e g e l , L . A . < / A U T H O R > < A U T H O R > C h e s n e y , J . < / A U T H O R > < A U T H O R > H o g a n , M . < / A U T H O R > < A U T H O R > C e r a m i , A . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > M o l M e d < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > A n t i g e n s , C D 4 / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > B a s e S e q u e n c e < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w / r a d i a t i o n e f f e c t s < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s < / K E Y W O R D > < K E Y W O R D > C e l l A d h e s i o n < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C e n t r i f u g a t i o n < / K E Y W O R D > < K E Y W O R D > C h i m e r a < / K E Y W O R D > < K E Y W O R D > C o l l a g e n / c h e m i s t r y / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > C o n n e c t i v e T i s s u e / b l o o d s u p p l y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > C y t o s k e l e t o n < / K E Y W O R D > < K E Y W O R D > D N A - B i n d i n g P r o t e i n s / g e n e t i c s < / K E Y W O R D > < K E Y W O R D > D o s e - R e s p o n s e R e l a t i o n s h i p , R a d i a t i o n < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > F i b r o b l a s t s / c h e m i s t r y / c y t o l o g y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > F l o w C y t o m e t r y / m e t h o d s < / K E Y W O R D > < K E Y W O R D > F l u o r e s c e n t A n t i b o d y T e c h n i q u e < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > I m m u n o h i s t o c h e m i s t r y < / K E Y W O R D > < K E Y W O R D > L e u k o c y t e s / * c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d B A L B C < / K E Y W O R D > < K E Y W O R D > M i c r o s c o p y , E l e c t r o n < / K E Y W O R D > < K E Y W O R D > M o l e c u l a r S e q u e n c e D a t a < / K E Y W O R D > < K E Y W O R D > * N u c l e a r P r o t e i n s < / K E Y W O R D > < K E Y W O R D > P h e n o t y p e < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S e x - D e t e r m i n i n g R e g i o n Y P r o t e i n < / K E Y W O R D > < K E Y W O R D > T i m e F a c t o r s < / K E Y W O R D > < K E Y W O R D > * T r a n s c r i p t i o n F a c t o r s < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n , H e t e r o l o g o u s < / K E Y W O R D > < K E Y W O R D > V i m e n t i n / c h e m i s t r y < / K E Y W O R D > < K E Y W O R D > W o u n d H e a l i n g / * p h y s i o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 8 7 9 0 6 0 3 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 3 3 ) . D r u g a m o g u n o s t s u s t a n i c e k o j e p o d r ~a v a j u h e m a t o p o e t s k e e l e m e n t e u k o at a n o j s r ~i A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > Z h a n g < / A u t h o r > < Y e a r > 2 0 0 4 < / Y e a r > < R e c N u m > 8 0 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 5 5 7 9 6 4 4 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 2 < / V O L U M E > < N U M B E R > 7 < / N U M B E R > < Y E A R > 2 0 0 4 < / Y E A R > < T I T L E > S i m u l t a n e o u s i n j e c t i o n o f b o n e m a r r o w c e l l s a n d s t r o m a l c e l l s i n t o b o n e m a r r o w a c c e l e r a t e s h e m a t o p o i e s i s i n v i v o < / T I T L E > < P A G E S > 1 2 5 6 - 6 2 < / P A G E S > < A U T H O R _ A D D R E S S > F i r s t D e p a r t m e n t o f P a t h o l o g y , K a n s a i M e d i c a l U n i v e r s i t y , M o r i g u c h i , J a p a n . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > Z h a n g , Y . < / A U T H O R > < A U T H O R > A d a c h i , Y . < / A U T H O R > < A U T H O R > S u z u k i , Y . < / A U T H O R > < A U T H O R > M i n a m i n o , K . < / A U T H O R > < A U T H O R > I w a s a k i , M . < / A U T H O R > < A U T H O R > H i s h a , H . < / A U T H O R > < A U T H O R > S o n g , C . Y . < / A U T H O R > < A U T H O R > K u s a f u k a , K . < / A U T H O R > < A U T H O R > N a k a n o , K . < / A U T H O R > < A U T H O R > K o i k e , Y . < / A U T H O R > < A U T H O R > W a n g , J . < / A U T H O R > < A U T H O R > K o h , E . < / A U T H O R > < A U T H O R > C u i , Y . < / A U T H O R > < A U T H O R > L i , C . < / A U T H O R > < A U T H O R > I k e h a r a , S . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > S t e m C e l l s < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > B o n e M a r r o w C e l l s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w T r a n s p l a n t a t i o n / * m e t h o d s < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l L i n e a g e < / K E Y W O R D > < K E Y W O R D > C e l l s , C u l t u r e d < / K E Y W O R D > < K E Y W O R D > C h o n d r o c y t e s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > C l u s t e r A n a l y s i s < / K E Y W O R D > < K E Y W O R D > D N A P r i m e r s / c h e m i s t r y < / K E Y W O R D > < K E Y W O R D > E n d o t h e l i u m , V a s c u l a r / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > F l o w C y t o m e t r y < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e s i s < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > L e u k o c y t e s / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > M e s o d e r m / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > N e o v a s c u l a r i z a t i o n , P h y s i o l o g i c < / K E Y W O R D > < K E Y W O R D > P h y l o g e n y < / K E Y W O R D > < K E Y W O R D > R N A , M e s s e n g e r / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e v e r s e T r a n s c r i p t a s e P o l y m e r a s e C h a i n R e a c t i o n < / K E Y W O R D > < K E Y W O R D > S o f t w a r e < / K E Y W O R D > < K E Y W O R D > S t e m C e l l s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / * c y t o l o g y < / K E Y W O R D > < K E Y W O R D > U m b i l i c a l C o r d / c y t o l o g y < / K E Y W O R D > < K E Y W O R D > U m b i l i c a l V e i n s / * c y t o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 5 5 7 9 6 4 4 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 3 4 ) . N j i h o v o v r e m e n s k o p o j a v l j i v a n j e p o v e z a n o s a s t v a r a n j e m k o at a n e s r ~i t e n j i h o v a s p o s o b n o s t e n g r a f t m e n t a p u t e m c i r k u l a c i j e s u k l a d n a j e s o v o m u l o g o m . O v e G F P p o z i t i v n e s t a n i c e t a k o e r s u o p a ~e n e n a e n d o s t e l n o j p o v r ai n i c i j e l o g s k e l e t a u m i ae v a p o d v r g n u t i m a T O T / K K S p r o t o k o l u r a d i p r o c j e n e o s t e o g e n e a k t i v n o s t i p r o g e n i t o r s k i h s t a n i c a n a k o n i n j e k c i j e u k o at a n u s r ~ A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > W a n g < / A u t h o r > < Y e a r > 2 0 0 5 < / Y e a r > < R e c N u m > 1 3 4 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 6 0 8 1 6 9 4 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 0 6 < / V O L U M E > < N U M B E R > 1 0 < / N U M B E R > < Y E A R > 2 0 0 5 < / Y E A R > < D A T E > N o v 1 5 < / D A T E > < T I T L E > H e t e r o g e n e i t y o f e n g r a f t e d b o n e - l i n i n g c e l l s a f t e r s y s t e m i c a n d l o c a l t r a n s p l a n t a t i o n < / T I T L E > < P A G E S > 3 6 5 0 - 7 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n , 0 6 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > W a n g , L . < / A U T H O R > < A U T H O R > L i u , Y . < / A U T H O R > < A U T H O R > K a l a j z i c , Z . < / A U T H O R > < A U T H O R > J i a n g , X . < / A U T H O R > < A U T H O R > R o w e , D . W . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B l o o d < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > * B o n e M a r r o w T r a n s p l a n t a t i o n / m e t h o d s < / K E Y W O R D > < K E Y W O R D > C a l c i f i c a t i o n , P h y s i o l o g i c / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > E x t r a c e l l u l a r M a t r i x / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > G e n e E x p r e s s i o n R e g u l a t i o n / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , T r a n s g e n i c < / K E Y W O R D > < K E Y W O R D > M o d e l s , A n i m a l < / K E Y W O R D > < K E Y W O R D > O r g a n S p e c i f i c i t y / p h y s i o l o g y / r a d i a t i o n e f f e c t s < / K E Y W O R D > < K E Y W O R D > O s t e o b l a s t s / c y t o l o g y / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > O s t e o g e n e s i s / * p h y s i o l o g y / r a d i a t i o n e f f e c t s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N . I . H . , E x t r a m u r a l < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > S k u l l / c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / c y t o l o g y / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n C h i m e r a / * p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > T r a n s p l a n t a t i o n , H o m o l o g o u s < / K E Y W O R D > < K E Y W O R D > W h o l e - B o d y I r r a d i a t i o n / m e t h o d s < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 6 0 8 1 6 9 4 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 2 5 ) . Z a r a z l i k u o d s t r o m a l n i h s t a n i c a k o j e o s t a j u o g r a n i
e n e u n u t a r i n j i c i r a n e k o s t i t e s u d j e l u j u u r e m o d e l i r a n j u k o s t i d o m a i n a , c i r k u l i r a j u e s t a n i c e n i s u p o v e z a n e s n o v o s t v o r e n i m o d l a g a n j e m m i n e r a l a ( p r o c i j e n j e n o k r o z o d l a g a n j e k s i l o l c r v e n e b o j e ) , n i t i u l a z e u k o at a n i m a t r i k s . N e d a v n o j e n a p r a v l j e n a s t u d i j a u k o j o j j e k o r i at e n s i s t e m p a r a b i o z e , g d j e j e p O B C o l 3 . 6 G F P t r a n s g e n i
n a ~i v o t i n j a b i l a k i r u r ak i s p o j e n a s C o l 2 . 3 T K t r a n s g e n i
n i m m i ae m A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > B o b a n < / A u t h o r > < Y e a r > 2 0 0 6 < / Y e a r > < R e c N u m > 1 5 0 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 6 9 3 8 4 9 7 < / A C C E S S I O N _ N U M B E R > < Y E A R > 2 0 0 6 < / Y E A R > < D A T E > A u g 2 6 < / D A T E > < T I T L E > T h e 3 . 6 k b D N A f r a g m e n t f r o m t h e r a t C o l 1 a 1 g e n e p r o m o t e r d r i v e s t h e e x p r e s s i o n o f g e n e s i n b o t h o s t e o b l a s t a n d o s t e o c l a s t l i n e a g e c e l l s < / T I T L E > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f G e n e t i c s a n d D e v e l o p m e n t a l B i o l o g y , U n i v e r s i t y o f C o n n e c t i c u t H e a l t h C e n t e r , F a r m i n g t o n , C T 0 6 0 3 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > B o b a n , I . < / A U T H O R > < A U T H O R > J a c q u i n , C . < / A U T H O R > < A U T H O R > P r i o r , K . < / A U T H O R > < A U T H O R > B a r i s i c - D u j m o v i c , T . < / A U T H O R > < A U T H O R > M a y e , P . < / A U T H O R > < A U T H O R > C l a r k , S . H . < / A U T H O R > < A U T H O R > A g u i l a , H . L . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B o n e < / S E C O N D A R Y _ T I T L E > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 6 9 3 8 4 9 7 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 3 5 ) . H i s t o l o g i j a k o s t i C o l 2 . 3 T K m i ae v a n a k o n G C V t r e t m a n a p o k a z a l a j e p r i s u s t v o G F P b i l j e g a n a e n d o s t e a l n o j i p e r i o s t e a l n o j p o v r ai n i . U B M S C k u l t u r a m a n i j e b i l o m i n e r a l i z i r a n i h k o l o n i j a s i z r a ~a j e m G F P - a , n o f l u o r e s c e n t n i b i l j e g j e o p a ~e n u s k u p o v i m a v e l i k i h s t a n i c a s l i
n i h o s t e k l a s t i m a k o j e s u b i l e T R A P p o z i t i v n e . B u d u i d a o s t e o k l a s t i p o t j e
u i z m i j e l o i d n e s t a n i
n e l o z e , p r o i z l a z i d a C o l 3 . 6 p r o m o t o r s a d r ~i e l e m e n t e k o j i s u a k t i v n i t i j e k o m o s t e o k l a s t o g e n e z e i k o j i n i s u s t r o g o o g r a n i
e n i n a t r a n s k r i p c i j u k o l a g e n a . D a k l e , t r e a m o g u n o s t b i b i l e p r e t e
e o s t e k l a s t i
n e l o z e k o j e i z r a ~a v a j u p O B C o l 3 . 6 G F P b i l j e g .
V I . Z A K L J U C I
M o ~e s e o
e k i v a t i d a m n o g i t r a n s g e n i
n i i k n o c k o u t m i aj i m o d e l i k o j i u t j e
u n a s t j e c a n j e k o at a n e m a s e d j e l u j u n a r a z l i
i t i m s t a d i j i m a o s t e o b l a s t i
n o g r a z v o j a . U p o r a b a b i l j e g g e n a p o d k o n t r o l o m o d r e e n o g t r a n s g e n a z a r a z l i
i t e s t a d i j e o s t e o b l a s t i
n o g r a z v o j a m o ~e p o m o i u o d r e i v a n j u m j e s t a u n u t a r s t a n i
n e l o z e g d j e m u t a c i j a i n t e r f e r i r a s a s a z r i j e v a n j e m k o at a n i h s t a n i c a , k a o at o j e t o n a p r a v l j e n o z a m u t a c i j e u n u t a r h e m a t o p o e t s k e l o z e A D D I N E N . C I T E < E n d N o t e > < C i t e > < A u t h o r > P a s s e g u e < / A u t h o r > < Y e a r > 2 0 0 3 < / Y e a r > < R e c N u m > 9 4 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 4 5 0 4 3 8 7 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 0 0 S u p p l 1 < / V O L U M E > < Y E A R > 2 0 0 3 < / Y E A R > < D A T E > S e p 3 0 < / D A T E > < T I T L E > N o r m a l a n d l e u k e m i c h e m a t o p o i e s i s : a r e l e u k e m i a s a s t e m c e l l d i s o r d e r o r a r e a c q u i s i t i o n o f s t e m c e l l c h a r a c t e r i s t i c s ? < / T I T L E > < P A G E S > 1 1 8 4 2 - 9 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f P a t h o l o g y , S t a n f o r d U n i v e r s i t y S c h o o l o f M e d i c i n e , S t a n f o r d , C A 9 4 3 0 5 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > P a s s e g u e , E . < / A U T H O R > < A U T H O R > J a m i e s o n , C . H . < / A U T H O R > < A U T H O R > A i l l e s , L . E . < / A U T H O R > < A U T H O R > W e i s s m a n , I . L . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > P r o c N a t l A c a d S c i U S A < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > A p o p t o s i s < / K E Y W O R D > < K E Y W O R D > C e l l D i f f e r e n t i a t i o n < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n < / K E Y W O R D > < K E Y W O R D > C e l l M e m b r a n e / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > * H e m a t o p o i e s i s < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > L e u k e m i a / g e n e t i c s / m e t a b o l i s m / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M o d e l s , B i o l o g i c a l < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < K E Y W O R D > T u m o r M a r k e r s , B i o l o g i c a l / m e t a b o l i s m < / K E Y W O R D > < K E Y W O R D > T u m o r S t e m C e l l s / m e t a b o l i s m / * p a t h o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 4 5 0 4 3 8 7 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > N i s h i m u r a < / A u t h o r > < Y e a r > 2 0 0 2 < / Y e a r > < R e c N u m > 9 2 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 2 4 9 0 2 8 2 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 2 9 < / V O L U M E > < N U M B E R > 2 < / N U M B E R > < Y E A R > 2 0 0 2 < / Y E A R > < D A T E > S e p - O c t < / D A T E > < T I T L E > T h e h e m a t o p o i e t i c d e f e c t i n P N H i s n o t d u e t o d e f e c t i v e s t r o m a , b u t i s d u e t o d e f e c t i v e p r o g e n i t o r c e l l s < / T I T L E > < P A G E S > 1 5 9 - 6 7 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f M e d i c i n e , D u k e U n i v e r s i t y M e d i c a l C e n t e r , D u r h a m , N o r t h C a r o l i n a 2 7 7 1 0 , U S A . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > N i s h i m u r a , J . < / A U T H O R > < A U T H O R > W a r e , R . E . < / A U T H O R > < A U T H O R > B u r n e t t e , A . < / A U T H O R > < A U T H O R > P e n d l e t o n , A . L . < / A U T H O R > < A U T H O R > K i t a n o , K . < / A U T H O R > < A U T H O R > H i r o t a , T . < / A U T H O R > < A U T H O R > M a c h i i , T . < / A U T H O R > < A U T H O R > K i t a n i , T . < / A U T H O R > < A U T H O R > S m i t h , C . A . < / A U T H O R > < A U T H O R > R o s s e , W . F . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B l o o d C e l l s M o l D i s < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A d u l t < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w C e l l s / p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > C a s e - C o n t r o l S t u d i e s < / K E Y W O R D > < K E Y W O R D > C e l l D i v i s i o n < / K E Y W O R D > < K E Y W O R D > C o c u l t u r e T e c h n i q u e s < / K E Y W O R D > < K E Y W O R D > C o l o n y - F o r m i n g U n i t s A s s a y < / K E Y W O R D > < K E Y W O R D > D y s p n e a , P a r o x y s m a l / e t i o l o g y / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > F e m a l e < / K E Y W O R D > < K E Y W O R D > G l y c o s y l p h o s p h a t i d y l i n o s i t o l s < / K E Y W O R D > < K E Y W O R D > * H e m a t o p o i e s i s < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > H u m a n s < / K E Y W O R D > < K E Y W O R D > M a l e < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > S t r o m a l C e l l s / * c y t o l o g y < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 2 4 9 0 2 8 2 < / U R L > < / M D L > < / C i t e > < C i t e > < A u t h o r > L i < / A u t h o r > < Y e a r > 2 0 0 3 < / Y e a r > < R e c N u m > 8 9 < / R e c N u m > < M D L > < R E F E R E N C E _ T Y P E > 0 < / R E F E R E N C E _ T Y P E > < A C C E S S I O N _ N U M B E R > 1 2 7 6 3 9 2 9 < / A C C E S S I O N _ N U M B E R > < V O L U M E > 1 0 2 < / V O L U M E > < N U M B E R > 6 < / N U M B E R > < Y E A R > 2 0 0 3 < / Y E A R > < D A T E > S e p 1 5 < / D A T E > < T I T L E > F a n c o n i a n e m i a t y p e C - d e f i c i e n t h e m a t o p o i e t i c s t e m / p r o g e n i t o r c e l l s e x h i b i t a b e r r a n t c e l l c y c l e c o n t r o l < / T I T L E > < P A G E S > 2 0 8 1 - 4 < / P A G E S > < A U T H O R _ A D D R E S S > D e p a r t m e n t o f P e d i a t r i c s , H e r m a n B . W e l l s C e n t e r f o r P e d i a t r i c R e s e a r c h , I n d i a n a U n i v e r s i t y S c h o o l o f M e d i c i n e , I n d i a n a p o l i s , I N 4 6 2 0 2 - 5 2 5 4 . < / A U T H O R _ A D D R E S S > < A U T H O R S > < A U T H O R > L i , X . < / A U T H O R > < A U T H O R > P l e t t , P . A . < / A U T H O R > < A U T H O R > Y a n g , Y . < / A U T H O R > < A U T H O R > H o n g , P . < / A U T H O R > < A U T H O R > F r e i e , B . < / A U T H O R > < A U T H O R > S r o u r , E . F . < / A U T H O R > < A U T H O R > O r s c h e l l , C . M . < / A U T H O R > < A U T H O R > C l a p p , D . W . < / A U T H O R > < A U T H O R > H a n e l i n e , L . S . < / A U T H O R > < / A U T H O R S > < S E C O N D A R Y _ T I T L E > B l o o d < / S E C O N D A R Y _ T I T L E > < K E Y W O R D S > < K E Y W O R D > A n i m a l s < / K E Y W O R D > < K E Y W O R D > A p o p t o s i s / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > B o n e M a r r o w / p a t h o l o g y / p h y s i o p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > C e l l C y c l e / p h y s i o l o g y < / K E Y W O R D > < K E Y W O R D > * C e l l C y c l e P r o t e i n s < / K E Y W O R D > < K E Y W O R D > * D N A - B i n d i n g P r o t e i n s < / K E Y W O R D > < K E Y W O R D > F a n c o n i A n e m i a / e t i o l o g y / * p a t h o l o g y / p h y s i o p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > F a n c o n i A n e m i a C o m p l e m e n t a t i o n G r o u p C P r o t e i n < / K E Y W O R D > < K E Y W O R D > F a n c o n i A n e m i a C o m p l e m e n t a t i o n G r o u p P r o t e i n s < / K E Y W O R D > < K E Y W O R D > H e m a t o p o i e t i c S t e m C e l l s / * p a t h o l o g y < / K E Y W O R D > < K E Y W O R D > M i c e < / K E Y W O R D > < K E Y W O R D > M i c e , I n b r e d C 5 7 B L < / K E Y W O R D > < K E Y W O R D > M i c e , M u t a n t S t r a i n s < / K E Y W O R D > < K E Y W O R D > * N u c l e a r P r o t e i n s < / K E Y W O R D > < K E Y W O R D > P h e n o t y p e < / K E Y W O R D > < K E Y W O R D > P r o t e i n s / * g e n e t i c s < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , N o n - U . S . G o v & a p o s ; t < / K E Y W O R D > < K E Y W O R D > R e s e a r c h S u p p o r t , U . S . G o v & a p o s ; t , P . H . S . < / K E Y W O R D > < / K E Y W O R D S > < U R L > h t t p : / / w w w . n c b i . n l m . n i h . g o v / e n t r e z / q u e r y . f c g i ? c m d = R e t r i e v e & a m p ; d b = P u b M e d & a m p ; d o p t = C i t a t i o n & a m p ; l i s t _ u i d s = 1 2 7 6 3 9 2 9 < / U R L > < / M D L > < / C i t e > < / E n d N o t e > ( 1 3 6 - 1 3 8 ) . D a k l e , d o s t u p n o s t z a j e d n i
k o g r e p e r t o a r a o k a r a k t e r i z i r a n i h b i l j e g g e n a k o j i p r e d s t a v l j a ai r o k i r a s p o n r a z v o j n i h s t a d i j a o s t e o b l a s t i
n e l o z e t r e b a o b i p o m o i u d e f i n i r a n j u m o l e k u l a r n i h i s t a n i
n i h d e t e r m i n a n t i n o r m a l n e k o at a n e b i o l o g i j e .
Z a k l j u
c i s t u d i j e a n a l i z e h e t e r o g e n o s t i p o p u l a c i j a o s t e o b l a s t a t i j e k o m p r o c e s a s t v a r a n j a k o at a n o g t k i v a :
H u m a n i o s t e o k a l c i n t r a n s g e n o b i l j e ~e n t o p a z v a r i j a n t o m G F P - a j e s t v r i j e d a n i r e p r o d u c i b i l a n b i l j e g p r i o b i l j e ~a v a n j u o s t e o b l a s t i
n e p o p u l a c i j e s e k s p r e s i j o m o s t e o k a l c i n a .
C y a n i n a
i c a p O B C o l 3 . 6 t r a n s g e n a p o s j e d u j e i s t u v r i j e d n o s t k o d o b i l j e ~a v a n j a p o p u l a c i j e p r e o s t e b l a s t a , k a o i n j e z i n p r e t h o d n i k p O B C o l 3 . 6 G F P t o p a z t r a n s g e n .
K r i ~a n j e m p O B C o l 3 . 6 G F P c y a n i h O C - G F P t p z t r a n s g e n i
n i h m i ae v a m o ~e m o i l u s t r i r a t i h e t e r o g e n o s t s t a n i
n e p o p u l a c i j e k o j a j e s t a n d a r d n i m h i s t o l o ak i m m e t o d a m a i m o l e k u l a r n i m o s o b i n a m a s v r s t a n a p o d j e d a n s t a d i j o s t e o b l a s t i
n e d i f e r e n c i j a c i j e .
H e t e r o t o p i
n a k o at a n a f o r m a c i j a s i n e r t n i m k o l a g e n s k i m n o s a
e m t e i m p l a n t a c i j o m u o z r a
e n o g i s p a ae n o g d o m a i n a s G F P o b i l j e ~e n i m d o n o r s k i m p o p u l a c i j a m a p r u ~a j e d n o s t a v a n , a l i b i t a n m o d e l z a i s t r a ~i v a n j e p r o g e n i t o r s k o g s t a t u s a s t a n i
n e p o p u l a c i j e i d o p r i n o s a
i m b e n i k a r a s t a u p r o c e s u s t v a r a n j a n o v e k o s t i . B M S C k o r i at e n e u o v o j s t u d i j i i m a l e s u e n d o t e l n i i o s t e o b l a s t i
n i p o t e n c i j a l z b o g m i j e aa n e p r i r o d e i m p l a n t a t a . O v a j m o d e l s e t a k o e r m o ~e k o r i s t i t i z a p r o c i j e n u r e l a t i v n o g o s t e o g e n o g p o t e n c i j a l a d v i j e p r o g e n i t o r s k e p o p u l a c i j e u n u t a r i m p l a n t a t a . M i j e aa j u i t e s t i k o n t r o l n e s k u p i n e p r o g e n i t o r s k i h p o p u l a c i j a o z n a
e n i h s r a z l i
i t i m G F P b i l j e z i m a , m o g u s e p r i m i j e n i t i k o m p e t i t i v n i i k o m p l e m e n t a r n i e k s p e r i m e n t a l n i d i z a j n i p r i i s t r a ~i v a n j u s t a n i
n i h a u t o n o m n i h i n e - a u t o n o m n i h p r o g e n i t o r a , t e
i m b e n i k a d o m a i n a k o j i u t j e
u n a k o at a n u f o r m a c i j u .
Z a k l j u
c i s t u d i j e h e t e r o t o p i
n e k o at a n e f o r m a c i j e :
C D 3 1 + e n d o t e l n e s t a n i c e u i m p l a n t a t u p o t j e
u o d d a v a t e l j a , a n e o d p r i m a t e l j a . D o m a i n n e p r i d o n o s i l o k a l n o m r a s t u e n d o t e l n i h s t a n i c a , n i t i s u e n d o t e l n e s t a n i c e u n u t a r k o at a n e s r ~i p o t e k l e o d d o m a i n a . D a k l e , d o m a i n o v e e n d o t e l n e s t a n i c e n e p r i d o n o s e a n g i o g e n e z i n i t i u r a s t a n j e m n i t i p u t e m c i r k u l a c i j e .
K o at a n a j e f o r m a c i j a a p s o l u t n o o v i s n a o d o n o r s k i m p r o g e n i t o r s k i m s t a n i c a m a j e r n i t i j e d a n o s t e o b l a s t p o d r i j e t l o m o d d o m a i n a n i j e o p a ~e n u h e t e r o t o p i
n o j k o s t i b i l o d i r e k t n o m i n v a z i j o m i l i p u t e m c i r k u l a c i j e .
O b l o ~n e s t a n i c e k o j e n e s u d j e l u j u u s t v a r a n j u n o v e k o s t i p o t j e
u o d d o m a i n a i l i K K S s t a n i c a . O n e b i m o g l e p r e d s t a v l j a t i h e t e r o g e n u p o p u l a c i j u r a n i h s t a d i j a p r e t e
a o s t e o k l a s t i
n e l o z e , c i r k u l i r a j u i h f i b r o b l a s t a i l i s t a n i c a k o j e p o d r ~a v a j u h e m a t o p o e z u .
K o r i at e n j e G F P t r a n s g e n i
n i h b i l j e g a p o k a z a l o j e k o r i s n o s t u i d e n t i f i c i r a n j u k a k o s t a n i c a r a z l i
i t i h s t a d i j a u n u t a r o s t e o b l a s t i
n e l o z e , t a k o i u m o d e l u h e t e r o t o p i
n e i m p l a n t a c i j e g d j e s e p o k a z a o k a o i z u z e t a n m o d e l k o j i m m o ~e m o p r a t i t i d o p r i n o s d o m a i n a i d o n o r a u s t v a r a n j u k o s t i , t e p o d r i j e t l o s t a n i c a o s t e o b l a s t i
n e l o z e i s t a n i c a n e o s t e o b l a s t i
n i h l o z a k o j e i m a j u i z u z e t n u v a ~n o s t u p r o c e s u s t v a r a n j a n o v e k o s t i .
.
V I I . S A }E T A K
C i l j i s t r a ~i v a n j a : A n a l i z i r a t i h e t e r o g e n o s t o s t e o b l a s t i
n e l o z e p o m o u h u m a n o g o s t e o k a l c i n s k o g p r o m o t o r a i at a k o r s k o g k o l a g e n t i p 1 a 1 p r o m o t o r a v e z a n i h s v i z u a l n o r a z l i
i t i m G F P v a r i j a n t a m a , t o p a z o m i c y a n - o m . D r u g i c i l j j e p r e d s t a v i t i m o d e l h e t e r o t o p i
n e i m p l a n t a c i j e k o j i k o r i s t F G F 2 p r o ai r e n u p o p u l a c i j u s t a n i c a k o at a n e s r ~i ( B M S C ) i z o l i r a n i h i z T i e 2 e G F P ( e n d o t e l n i b i l j e g ) i p O B C o l 3 . 6 G F P c y a n i t o p a z ( b i l j e g p r e o s t e o b l a s t a ) t r a n s g e n i
n i h m i ae v a d a b i s m o o c i j e n i l i p r i m a t e l j / d a v a t e l j v e z u m e u s t a n i c a m a k o j e s u d j e l u j u u p r o c e s u h e t e r o t o p i
n e k o at a n e f o r m a c i j e .
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i n i t i a n a l i z u h i s t o l o ak i h r e z o v a k o s t i , t e B M S C i m C O B k u l t u r a d o b i v e n i h i z k r i ~a n i h t r a n s g e n i
n i h m i aj i h l i n i j a p O B C o l 3 . 6 G F P c y a n X h O C - G F P t p z . D r u g i d i o s t u d i j e u k l j u
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i t e k o m b i n a c i j e T i e 2 e G F P , p O B C o l 3 . 6 G F P c y a n / t o p a z t r a n s g e n i
n i h ~i v o t i n j a k a o d o n o r a s t r o m a l n i h s t a n i c a ( B M S C ) , k o m p l e t n e k o at a n e s r ~i ( K K S ) , t e k a o d o m a i n a . K o l a g e n i z o l i r a n i z r e p a at a k o r a k o r i at e n j e k a o n o s a
d o n o r s k i h s t a n i c a , a i m p l a n t a c i j a j e u
i n j e n a u l e t a l n o o z r a
e n o m m i au s p a ae n o m K K S i n j e k c i j o m . 4 - 5 t j e d a n a n a k o n t o t a l n o g o z r a
e n j a t i j e l a ( T O T ) r a z v i l a s e d o b r o f o r m i r a n a k o s t s k o at a n o m s r ~i .
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i t a u z o r k a d v o s t r u k e e k s p r e s i j e t r a n s g e n a o p a ~a j u s e u s t a n i
n i m k o at a n i m k u l t u r a m a i u h i s t o l o ak i m r e z o v i m a k o s t i . N a ai r e z u l t a t i p o d r ~a v a j u i n t e r p r e t a c i j u d a j e j a k i i z r a ~a j p O B C o l 3 . 6 G F P c y a n b i l j e g a s m j e at e n u n o v o s t v o r e n i m o s t e o b l a s t i m a , d o k j e i s t o v r e m e n i j a k i i z r a ~a j p O B C o l 3 . 6 G F P c y a n i h O C - G F P t p z t r a n s g e n a v i d l j i v u o s t e o b l a s t i m a k o j i a k t i v n o p r o i z v o d e m a t r i k s . O s t e o b l a s t i s j a k i m i z r a ~a j e m h O C - G F P t p z i s l a b i m p O B C o l 3 . 6 G F P c y a n t a k o e r s u p r i s u t n i , t e m o g u , a l i i n e m o r a j u p r o i z v o d i t i m i n e r a l i z i r a n i m a t r i k s . E k s p e r i m e n t i h e t e r o t o p i
n e k o at a n e f o r m a c i j e p o k a z u j u d o m i n a c i j u s t a n i c a p o t e k l i h o d d o n o r a u s t v a r a n j u e n d o t e l a k r v n i h ~i l a k a o i u s t v a r a n j u n o v e k o s t i u i m p l a n t a t u . N a d a l j e , o b l o ~n e s t a n i c e n a e n d o s t e a l n o j p o v r ai n i n o v o s t v o r e n e k o at a n e s r ~i p o t e k l e s u o d K K S d o n o r a i l i d o m a i n a .
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a k : O v a j s l o ~e n i p r i s t u p o t k r i v a h e t e r o g e n o s t u n u t a r p o p u l a c i j e z r e l i h o s t e o b l a s t a , k o j u n e m o ~e m o o t k r i t i s a d a an j i m h i s t o l o ak i m m e t o d a m a , t e b i m o g a o b i t i k o r i s t a n k o d i d e n t i f i c i r a n j a i i z o l i r a n j a p o p u l a c i j a s t a n i c a o s t e o b l a s t i
n e l o z e u r a z l i
i t i m s t a d i j i m a d i f e r e n c i j a c i j e . U m o d e l u s t v a r a n j a h e t e r o t o p i
n e k o s t i F G F 2 p r o ai r e n e s t r o m a l n e s t a n i c e k o at a n e s r ~i s u i z v o r e n d o t e l n i h i o s t e o g e n i h p r o g e n i t o r s k i h s t a n i c a s p o s o b n i h z a s t v a r a n j e n o v e k o s t i n e o v i s n o o d o m a i n u . O v a j e m o d e l b i t i k o r i s t a n z a r a z u m i j e v a n j e i n t e r a k c i j a i z m e u o v a d v a s t a n i
n a t i p a k o j i k o n t r o l i r a j u o s t e o b l a s t i
n u d i f e r e n c i j a c i j u i n v i v o .
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i : z e l e n a f l u o r e s c e n t a b j e l a n
e v i n a ( G F P ) , p r o m o t o r g e n a o s t e o k a l c i n a , p r o m o t o r k o l a g e n a t i p a 1 , T i e 2 p r o m o t o r , h e t e r o t o p i
n a k o at a n a f o r m a c i j a , d i f e r e n c i j a c i j a s t a n i c a o s t e o b l a s t n e l o z e
V I I I . S U M M A R Y
S t u d i i n g n e w b o n e f o r m a t i o n u s i n g t r a n s g e n i c m i c e w i t h v i s u a l m a r k e r s o f o s t e o b l a s t d i f f e r e n t i a t i o n
O b j e c t i v e s : M u l t i p l e x a n a l y s i s o f o s t e o b l a s t l i n e a g e p r o g r e s s i o n u s i n g h u m a n o s t e o c a l c i n p r o m o t e r a n d r a t c o l l a g e n t y p e 1 a 1 p r o m o t e r l i n k e d w i t h v i s u a l l y d i s t i n g u i s h a b l e G F P i s o m e r s , t o p a z a n d c y a n . S e c o n d o b j e c t i v e i s h e t e r o t o p i c i m p l a n t m o d e l u s i n g F G F - 2 e x p a n d e d b o n e m a r r o w s t r o m a l c e l l s ( B M S C ) d e r i v e d f r o m T i e 2 e G F P ( e n d o t h e l i a l m a r k e r ) a n d p O B C o l 3 . 6 G F P c y a n o r t o p a z ( e a r l y o s t e o b l a s t m a r k e r ) t r a n s g e n i c m i c e t o a p p r e c i a t e t h e h o s t / d o n o r r e l a t i o n s h i p s o f c e l l s p a r t i c i p a t i n g i n t h e p r o c e s s o f h e t e r o t o p i c b o n e f o r m a t i o n .
S t u d y d e s i g n : A n a l y s i s o f b o n e h i s t o l o g y a n d B M S C a n d m C O B p r i m a r y c e l l c u l t u r e s d e r i v e d f r o m p O B C o l 3 . 6 G F P c y a n X h O C - G F P t p z t r a n s g e n i c m i c e . T h e h e t e r o t o p i c b o n e f o r m a t i o n s t u d y i n c l u d e d v a r i o u s c o m b i n a t i o n s o f T i e 2 e G F P a n d p O B C o l 3 . 6 G F P c y a n a n d t o p a z t r a n s g e n i c s a s B M S C o r w h o l e b o n e m a r r o w ( W B M ) d o n o r s a n d a l s o a s r e c i p i e n t s . R a t - t a i l c o l l a g e n w a s u s e d a s a c a r r i e r o f d o n o r c e l l s a n d i m p l a n t a t i o n w a s d o n e i n l e t h a l l y i r r a d i a t e d m i c e r e s c u e d w i t h W B M i n j e c t i o n . F o u r t o f i v e w e e k s a f t e r t o t a l b o d y i r r a d i a t i o n ( T B I ) a n d i m p l a n t a t i o n , t h e r e s u l t i n g b o n e s p i c u l e w a s i n v e s t e d w i t h b o n e m a r r o w .
R e s u l t s : T h r e e p a t t e r n s o f d u a l t r a n s g e n e e x p r e s s i o n c a n b e a p p r e c i a t e d i n p r i m a r y b o n e c e l l c u l t u r e s d e r i v e d f r o m t h e t r a n s g e n i c m i c e a n d b y h i s t o l o g y o f t h e i r c o r r e s p o n d i n g b o n e s . O u r d a t a s u p p o r t t h e i n t e r p r e t a t i o n t h a t s t r o n g p O B C o l 3 . 6 G F P c y a n a l o n e i s f o u n d i n n e w l y f o r m e d o s t e o b l a s t s , w h i l e s t r o n g p O B C o l 3 . 6 G F P c y a n a n d h O C - G F P t p z a r e p r e s e n t i n o s t e o b l a s t s a c t i v e l y m a k i n g a n e w m a t r i x . O s t e o b l a s t s e x p r e s s i n g s t r o n g h O C - G F P t p z a n d w e a k p O B C o l 3 . 6 G F P c y a n a r e a l s o p r e s e n t a n d m a y o r m a y n o t b e p r o d u c i n g m i n e r a l i z e d m a t r i x . E x p e r i m e n t s s h o w e d a b s o l u t e d o m i n a n c e o f d o n o r d e r i v e d c e l l s i n t h e f o r m a t i o n o f e n d o t h e l i a l - l i n e d v e s s e l s i n s i d e t h e i m p l a n t s a s w e l l a s t h e m a r r o w s t r o m a l d e r i v e d o s t e o g e n i c c e l l s . I n a d d i t i o n , c e l l s l i n i n g t h e e n d o s t e a l s u r f a c e o f n e w l y f o r m e d m a r r o w s p a c e w e r e o b s e r v e d t h a t w e r e c o n t r i b u t e d b y W B M d o n o r c e l l s a n d t h e h o s t .
C o n c l u s i o n s : T h i s m u l t i p l e x a p p r o a c h r e v e a l s t h e h e t e r o g e n e i t y w i t h i n t h e m a t u r e o s t e o b l a s t p o p u l a t i o n t h a t c a n n o t b e a p p r e c i a t e d b y c u r r e n t h i s t o l o g i c a l m e t h o d s . I t s h o u l d b e u s e f u l t o i d e n t i f y a n d i s o l a t e p o p u l a t i o n s o f c e l l s w i t h i n a n o s t e o b l a s t l i n e a g e a s t h e y p r o g r e s s t h r o u g h s t a g e s o f d i f f e r e n t i a t i o n . I n t h e m o d e l o f h e t e r o t o p i c b o n e f o r m a t i o n , F G F - 2 e x p a n d e d B M S C a p p e a r t o b e a s o u r c e o f e n d o t h e l i a l a n d o s t e o g e n i c p r o g e n i t o r c e l l s c a p a b l e o f e l i c i t i n g h e t e r o t o p i c b o n e f o r m a t i o n i n d e p e n d e n t o f c e l l s f r o m t h e h o s t . T h i s m o d e l s h o u l d b e u s e f u l f o r u n d e r s t a n d i n g t h e i n t e r a c t i o n s b e t w e e n t h e s e t w o c e l l t y p e s t h a t c o n t r o l o s t e o g e n i c d i f f e r e n t i a t i o n i n v i v o .
K e y w o r d s : g r e e n f l o u r e s c e n t p r o t e i n ( G F P ) , o s t e o c a l c i n p r o m o t e r , T i e 2 p r o m o t e r , t y p e 1 c o l l a g e n p r o m o t e r , h e t e r o t o p i c b o n e f o r m a t i o n , o s t e o b l a s t d i f f e r e n t i a t i o n
I X . L I T E R A T U R A
A D D I N E N . R E F L I S T 1 . B a r o n , E . A n a t o m y a n d U l t r a s t r u c t i r e o f B o n e . I n : M . J . F a v u s ( e d . ) , P r i m e r o n t h e M e t a b o l i c B o n e D i s e a s e s a n d D i s o r d e r s o f M i n e r a l M e t a b o l i s m , p p . 3 - 1 1 . P h i l a d e l p h i a - N e w Y o r k : L i p p i n c o t t - R a v e n ; 1 9 9 6 .
2 . N i j w e i d e , P . J . , B u r g e r , E . H . , F e y e n , J . H . C e l l s o f b o n e : p r o l i f e r a t i o n , d i f f e r e n t i a t i o n , a n d h o r m o n a l r e g u l a t i o n . P h y s i o l R e v 6 6 : 8 5 5 - 8 6 ; 1 9 8 6 .
3 . J e e , W . T h e S k e l e t a l T i s s u e s . H i s t o l o g y , C e l l a n d T i s s u e B i o l o g y . N e w Y o r k : E l s e v i e r B i o m e d i c a l ; 1 9 8 3 .
4 . B a r o n , E . B i o l o g y o f t h e O s t e o c l a s t . P h y s i o l o g y a n d P h a r m a c o l o g y o f B o n e . N e w Y o r k : S p r i n g e r - V e r l a g ; 1 9 9 3 .
5 . A n n a b i , B . , N a u d , E . , L e e , Y . T . , E l i o p o u l o s , N . , G a l i p e a u , J . V a s c u l a r p r o g e n i t o r s d e r i v e d f r o m m u r i n e b o n e m a r r o w s t r o m a l c e l l s a r e r e g u l a t e d b y f i b r o b l a s t g r o w t h f a c t o r a n d a r e a v i d l y r e c r u i t e d b y v a s c u l a r i z i n g t u m o r s . J C e l l B i o c h e m 9 1 : 1 1 4 6 - 5 8 ; 2 0 0 4 .
6 . I m a n i s h i , T . , H a n o , T . , N i s h i o , I . A n g i o t e n s i n I I p o t e n t i a t e s v a s c u l a r e n d o t h e l i a l g r o w t h f a c t o r - i n d u c e d p r o l i f e r a t i o n a n d n e t w o r k f o r m a t i o n o f e n d o t h e l i a l p r o g e n i t o r c e l l s . H y p e r t e n s R e s 2 7 : 1 0 1 - 8 ; 2 0 0 4 .
7 . K a i g l e r , D . , K r e b s b a c h , P . H . , P o l v e r i n i , P . J . , M o o n e y , D . J . R o l e o f v a s c u l a r e n d o t h e l i a l g r o w t h f a c t o r i n b o n e m a r r o w s t r o m a l c e l l m o d u l a t i o n o f e n d o t h e l i a l c e l l s . T i s s u e E n g 9 : 9 5 - 1 0 3 ; 2 0 0 3 .
8 . T o m b r a n - T i n k , J . , B a r n s t a b l e , C . J . O s t e o b l a s t s a n d o s t e o c l a s t s e x p r e s s P E D F , V E G F - A i s o f o r m s , a n d V E G F r e c e p t o r s : p o s s i b l e m e d i a t o r s o f a n g i o g e n e s i s a n d m a t r i x r e m o d e l i n g i n t h e b o n e . B i o c h e m B i o p h y s R e s C o m m u n 3 1 6 : 5 7 3 - 9 ; 2 0 0 4 .
9 . A n n a b i , B . , L e e , Y . T . , T u r c o t t e , S . , N a u d , E . , D e s r o s i e r s , R . R . , C h a m p a g n e , M . , i s u r . H y p o x i a p r o m o t e s m u r i n e b o n e - m a r r o w - d e r i v e d s t r o m a l c e l l m i g r a t i o n a n d t u b e f o r m a t i o n . S t e m C e l l s 2 1 : 3 3 7 - 4 7 ; 2 0 0 3 .
1 0 . K o m a t s u , D . E . , H a d j i a r g y r o u , M . A c t i v a t i o n o f t h e t r a n s c r i p t i o n f a c t o r H I F - 1 a n d i t s t a r g e t g e n e s , V E G F , H O - 1 , i N O S , d u r i n g f r a c t u r e r e p a i r . B o n e 3 4 : 6 8 0 - 8 ; 2 0 0 4 .
1 1 . Z e b b o u d j , A . F . , S h i n , V . , B o s t r o m , K . M a t r i x G L A p r o t e i n a n d B M P - 2 r e g u l a t e o s t e o i n d u c t i o n i n c a l c i f y i n g v a s c u l a r c e l l s . J C e l l B i o c h e m 9 0 : 7 5 6 - 6 5 ; 2 0 0 3 .
1 2 . V e i l l e t t e , C . J . , v o n S c h r o e d e r , H . P . E n d o t h e l i n - 1 d o w n - r e g u l a t e s t h e e x p r e s s i o n o f v a s c u l a r e n d o t h e l i a l g r o w t h f a c t o r - A a s s o c i a t e d w i t h o s t e o p r o g e n i t o r p r o l i f e r a t i o n a n d d i f f e r e n t i a t i o n . B o n e 3 4 : 2 8 8 - 9 6 ; 2 0 0 4 .
1 3 . v o n S c h r o e d e r , H . P . , V e i l l e t t e , C . J . , P a y a n d e h , J . , Q u r e s h i , A . , H e e r s c h e , J . N . E n d o t h e l i n - 1 p r o m o t e s o s t e o p r o g e n i t o r p r o l i f e r a t i o n a n d d i f f e r e n t i a t i o n i n f e t a l r a t c a l v a r i a l c e l l c u l t u r e s . B o n e 3 3 : 6 7 3 - 8 4 ; 2 0 0 3 .
1 4 . H e n r i k s e n , K . , K a r s d a l , M . , D e l a i s s e , J . M . , E n g s i g , M . T . R A N K L a n d v a s c u l a r e n d o t h e l i a l g r o w t h f a c t o r ( V E G F ) i n d u c e o s t e o c l a s t c h e m o t a x i s t h r o u g h a n E R K 1 / 2 - d e p e n d e n t m e c h a n i s m . J B i o l C h e m 2 7 8 : 4 8 7 4 5 - 5 3 ; 2 0 0 3 .
1 5 . P u z a s , J . O s t e o b l a s t C e l l B i o l o g y - L i n e a g e a n d F u n c t i o n s . I n : M . J . F a v u s ( e d . ) , P r i m e r o n t h e M e t a b o l i c B o n e D i s e a s e s a n d D i s o r d e r s o f M i n e r a l M e t a b o l i s m , p p . 1 1 - 1 6 . P h i l a d e l p h i a - N e w Y o r k : L i p p i n c o t t - R a v e n ; 1 9 9 6 .
1 6 . O w e n , M . M a r r o w s t r o m a l s t e m c e l l s . J C e l l S c i S u p p l 1 0 : 6 3 - 7 6 ; 1 9 8 8 .
1 7 . A u b i n , J . E . , L i u , F . , M a l a v a l , L . , G u p t a , A . K . O s t e o b l a s t a n d c h o n d r o b l a s t d i f f e r e n t i a t i o n . B o n e 1 7 : 7 7 S - 8 3 S ; 1 9 9 5 .
1 8 . F r i e d e n s t e i n , A . J . , C h a i l a k h y a n , R . K . , L a t s i n i k , N . V . , P a n a s y u k , A . F . , K e i l i s s - B o r o k , I . V . S t r o m a l c e l l s r e s p o n s i b l e f o r t r a n s f e r r i n g t h e m i c r o e n v i r o n m e n t o f t h e h e m o p o i e t i c t i s s u e s . C l o n i n g i n v i t r o a n d r e t r a n s p l a n t a t i o n i n v i v o . T r a n s p l a n t a t i o n 1 7 : 3 3 1 - 4 0 ; 1 9 7 4 .
1 9 . N i j w e i d e , P . J . , v a n d e r P l a s A . E m b r y o n i c c h i c k p e r i o s t e u m i n t i s s u e c u l t u r e : o s t e o i d f o r m a t i o n a n d c a l c i u m u p t a k e . P r o c K N e d A k a d W e t C 7 8 : 4 1 0 - 4 1 7 ; 1 9 7 5 .
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4 9 . Z a m b o n i n - Z a l l o n e , A . , T e t i , A . , G r a n o , M . , R u b i n a c c i , A . , A b b a d i n i , M . , G a b o l i , M . , i s u r . I m m u n o c y t o c h e m i c a l d i s t r i b u t i o n o f e x t r a c e l l u l a r m a t r i x r e c e p t o r s i n h u m a n o s t e o c l a s t s : a b e t a 3 i n t e g r i n i s c o l o c a l i z e d w i t h v i n c u l i n a n d t a l i n i n t h e p o d o s o m e s o f o s t e o c l a s t o m a g i a n t c e l l s . E x p C e l l R e s 1 8 2 : 6 4 5 - 5 2 ; 1 9 8 9 .
5 0 . P r i c e , P . V i t a m i n K - d e p e n d a n t b o n e p r o t e i n s . I n : D . C o h n ( e d . ) , C a l c i u m R e g u l a t i o n a n d B o n e M e t a b o l i s m : B a s i c a n d C l i n i c a l A s p e c t s 9 , p p . 4 1 9 - 4 2 5 . A m s t e r d a m : E l s e v i e r S c i e n c e ; 1 9 8 7 .
5 1 . M a i l l a r d , C . , B e r r u y e r , M . , S e r r e , C . M . , D e c h a v a n n e , M . , D e l m a s , P . D . P r o t e i n - S , a v i t a m i n K - d e p e n d e n t p r o t e i n , i s a b o n e m a t r i x c o m p o n e n t s y n t h e s i z e d a n d s e c r e t e d b y o s t e o b l a s t s . E n d o c r i n o l o g y 1 3 0 : 1 5 9 9 - 6 0 4 ; 1 9 9 2 .
5 2 . K a s a i , R . , B i a n c o , P . , R o b e y , P . G . , K a h n , A . J . P r o d u c t i o n a n d c h a r a c t e r i z a t i o n o f a n a n t i b o d y a g a i n s t t h e h u m a n b o n e G L A p r o t e i n ( B G P / o s t e o c a l c i n ) p r o p e p t i d e a n d i t s u s e i n i m m u n o c y t o c h e m i s t r y o f b o n e c e l l s . B o n e M i n e r 2 5 : 1 6 7 - 8 2 ; 1 9 9 4 .
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6 4 . A u b i n J . E . , K . A . T h e o s t e o b l a s t l i n e a g e - e m b r y o l o g i c o r i g i n s a n d t h e d i f f e r e n t i a t i o n s e q u e n c e . I n : M . J . F a v u s ( e d . ) , P r i m e r o n t h e M e t a b o l i c B o n e D i s e a s e s a n d D i s o r d e r s o f M i n e r a l M e t a b o l i s m , p p . 3 5 - 3 8 . P h i l a d e l p h i a - N e w Y o r k : L i p p i n c o t t - R a v e n ; 1 9 9 6 .
6 5 . L i u , F . , M a l a v a l , L . , G u p t a , A . K . , A u b i n , J . E . S i m u l t a n e o u s d e t e c t i o n o f m u l t i p l e b o n e - r e l a t e d m R N A s a n d p r o t e i n e x p r e s s i o n d u r i n g o s t e o b l a s t d i f f e r e n t i a t i o n : p o l y m e r a s e c h a i n r e a c t i o n a n d i m m u n o c y t o c h e m i c a l s t u d i e s a t t h e s i n g l e c e l l l e v e l . D e v B i o l 1 6 6 : 2 2 0 - 3 4 ; 1 9 9 4 .
6 6 . B o m b i , J . A . , R i b a s - M u j a l , D . , T r u e t a , J . A n e l e c t r o n m i c r o s c o p i c s t u d y o f t h e o r i g i n o f o s t e o b l a s t s i n i m p l a n t s o f d e m i n e r a l i z e d b o n e m a t r i x . C l i n O r t h o p R e l a t R e s : 2 7 3 - 8 4 ; 1 9 7 8 .
6 7 . H e y m a n n , D . , T o u c h a i s , S . , B o h i c , S . , R o h a n i z a d e h , R . , C o q u a r d , C . , P a s s u t i , N . , i s u r . H e t e r o t o p i c i m p l a n t a t i o n o f m o u s e b o n e - m a r r o w c e l l s : a n i n v i v o m o d e l a l l o w i n g a n a l y s i s o f m i n e r a l p h a s e s d u r i n g m i n e r a l i z a t i o n p r o c e s s e s . C o n n e c t T i s s u e R e s 3 7 : 2 1 9 - 3 1 ; 1 9 9 8 .
6 8 . K r e b s b a c h , P . H . , K u z n e t s o v , S . A . , S a t o m u r a , K . , E m m o n s , R . V . , R o w e , D . W . , R o b e y , P . G . B o n e f o r m a t i o n i n v i v o : c o m p a r i s o n o f o s t e o g e n e s i s b y t r a n s p l a n t e d m o u s e a n d h u m a n m a r r o w s t r o m a l f i b r o b l a s t s . T r a n s p l a n t a t i o n 6 3 : 1 0 5 9 - 6 9 ; 1 9 9 7 .
6 9 . R u t h e r f o r d , R . B . , M o a l l i , M . , F r a n c e s c h i , R . T . , W a n g , D . , G u , K . , K r e b s b a c h , P . H . B o n e m o r p h o g e n e t i c p r o t e i n - t r a n s d u c e d h u m a n f i b r o b l a s t s c o n v e r t t o o s t e o b l a s t s a n d f o r m b o n e i n v i v o . T i s s u e E n g 8 : 4 4 1 - 5 2 ; 2 0 0 2 .
7 0 . G i m b l e , J . M . , R o b i n s o n , C . E . , W u , X . , K e l l y , K . A . , R o d r i g u e z , B . R . , K l i e w e r , S . A . , i s u r . P e r o x i s o m e p r o l i f e r a t o r - a c t i v a t e d r e c e p t o r - g a m m a a c t i v a t i o n b y t h i a z o l i d i n e d i o n e s i n d u c e s a d i p o g e n e s i s i n b o n e m a r r o w s t r o m a l c e l l s . M o l P h a r m a c o l 5 0 : 1 0 8 7 - 9 4 ; 1 9 9 6 .
7 1 . C h o i , K . T h e h e m a n g i o b l a s t : a c o m m o n p r o g e n i t o r o f h e m a t o p o i e t i c a n d e n d o t h e l i a l c e l l s . J H e m a t o t h e r S t e m C e l l R e s 1 1 : 9 1 - 1 0 1 ; 2 0 0 2 .
7 2 . H i r s c h i , K . K . , G o o d e l l , M . A . H e m a t o p o i e t i c , v a s c u l a r a n d c a r d i a c f a t e s o f b o n e m a r r o w - d e r i v e d s t e m c e l l s . G e n e T h e r 9 : 6 4 8 - 5 2 ; 2 0 0 2 .
7 3 . S h i n , V . , Z e b b o u d j , A . F . , B o s t r o m , K . E n d o t h e l i a l c e l l s m o d u l a t e o s t e o g e n e s i s i n c a l c i f y i n g v a s c u l a r c e l l s . J V a s c R e s 4 1 : 1 9 3 - 2 0 1 ; 2 0 0 4 .
7 4 . M i d y , V . , P l o u e t , J . V a s c u l o t r o p i n / v a s c u l a r e n d o t h e l i a l g r o w t h f a c t o r i n d u c e s d i f f e r e n t i a t i o n i n c u l t u r e d o s t e o b l a s t s . B i o c h e m B i o p h y s R e s C o m m u n 1 9 9 : 3 8 0 - 6 ; 1 9 9 4 .
7 5 . W a n g , D . S . , M i u r a , M . , D e m u r a , H . , S a t o , K . A n a b o l i c e f f e c t s o f 1 , 2 5 - d i h y d r o x y v i t a m i n D 3 o n o s t e o b l a s t s a r e e n h a n c e d b y v a s c u l a r e n d o t h e l i a l g r o w t h f a c t o r p r o d u c e d b y o s t e o b l a s t s a n d b y g r o w t h f a c t o r s p r o d u c e d b y e n d o t h e l i a l c e l l s . E n d o c r i n o l o g y 1 3 8 : 2 9 5 3 - 6 2 ; 1 9 9 7 .
7 6 . M a e s , C . , C a r m e l i e t , P . , M o e r m a n s , K . , S t o c k m a n s , I . , S m e t s , N . , C o l l e n , D . , i s u r . I m p a i r e d a n g i o g e n e s i s a n d e n d o c h o n d r a l b o n e f o r m a t i o n i n m i c e l a c k i n g t h e v a s c u l a r e n d o t h e l i a l g r o w t h f a c t o r i s o f o r m s V E G F 1 6 4 a n d V E G F 1 8 8 . M e c h D e v 1 1 1 : 6 1 - 7 3 ; 2 0 0 2 .
7 7 . Z e l z e r , E . , M c L e a n , W . , N g , Y . S . , F u k a i , N . , R e g i n a t o , A . M . , L o v e j o y , S . , i s u r . S k e l e t a l d e f e c t s i n V E G F ( 1 2 0 / 1 2 0 ) m i c e r e v e a l m u l t i p l e r o l e s f o r V E G F i n s k e l e t o g e n e s i s . D e v e l o p m e n t 1 2 9 : 1 8 9 3 - 9 0 4 ; 2 0 0 2 .
7 8 . V a n d e r s t e e n h o v e n , J . J . , D e L u s t r o , F . A . , B e l l , N . H . , T u r n e r , R . T . O s t e o i n d u c t i o n b y i m p l a n t s o f d e m i n e r a l i z e d a l l o g e n e i c b o n e m a t r i x i s d i m i n i s h e d i n v i t a m i n D - d e f i c i e n t r a t s . C a l c i f T i s s u e I n t 4 2 : 3 9 - 4 5 ; 1 9 8 8 .
7 9 . S e e h e r m a n , H . J . , B o u x s e i n , M . , K i m , H . , L i , R . , L i , X . J . , A i o l o v a , M . , i s u r . R e c o m b i n a n t h u m a n b o n e m o r p h o g e n e t i c p r o t e i n - 2 d e l i v e r e d i n a n i n j e c t a b l e c a l c i u m p h o s p h a t e p a s t e a c c e l e r a t e s o s t e o t o m y - s i t e h e a l i n g i n a n o n h u m a n p r i m a t e m o d e l . J B o n e J o i n t S u r g A m 8 6 - A : 1 9 6 1 - 7 2 ; 2 0 0 4 .
8 0 . A k a m a r u , T . , S u h , D . , B o d e n , S . D . , K i m , H . S . , M i n a m i d e , A . , L o u i s - U g b o , J . S i m p l e c a r r i e r m a t r i x m o d i f i c a t i o n s c a n e n h a n c e d e l i v e r y o f r e c o m b i n a n t h u m a n b o n e m o r p h o g e n e t i c p r o t e i n - 2 f o r p o s t e r o l a t e r a l s p i n e f u s i o n . S p i n e 2 8 : 4 2 9 - 3 4 ; 2 0 0 3 .
8 1 . L a u r e n c i n , C . T . , A t t a w i a , M . A . , L u , L . Q . , B o r d e n , M . D . , L u , H . H . , G o r u m , W . J . , i s u r . P o l y ( l a c t i d e - c o - g l y c o l i d e ) / h y d r o x y a p a t i t e d e l i v e r y o f B M P - 2 - p r o d u c i n g c e l l s : a r e g i o n a l g e n e t h e r a p y a p p r o a c h t o b o n e r e g e n e r a t i o n . B i o m a t e r i a l s 2 2 : 1 2 7 1 - 7 ; 2 0 0 1 .
8 2 . A s h t o n , B . A . , A l l e n , T . D . , H o w l e t t , C . R . , E a g l e s o m , C . C . , H a t t o r i , A . , O w e n , M . F o r m a t i o n o f b o n e a n d c a r t i l a g e b y m a r r o w s t r o m a l c e l l s i n d i f f u s i o n c h a m b e r s i n v i v o . C l i n O r t h o p R e l a t R e s : 2 9 4 - 3 0 7 ; 1 9 8 0 .
8 3 . A l - K h a l d i , A . , E l i o p o u l o s , N . , M a r t i n e a u , D . , L e j e u n e , L . , L a c h a p e l l e , K . , G a l i p e a u , J . P o s t n a t a l b o n e m a r r o w s t r o m a l c e l l s e l i c i t a p o t e n t V E G F - d e p e n d e n t n e o a n g i o g e n i c r e s p o n s e i n v i v o . G e n e T h e r 1 0 : 6 2 1 - 9 ; 2 0 0 3 .
8 4 . V i l l a n u e v a , J . E . , N i m n i , M . E . P r o m o t i o n o f c a l v a r i a l c e l l o s t e o g e n e s i s b y e n d o t h e l i a l c e l l s . J B o n e M i n e r R e s 5 : 7 3 3 - 9 ; 1 9 9 0 .
8 5 . K y r i a k i d e s , T . R . , H a r t z e l , T . , H u y n h , G . , B o r n s t e i n , P . R e g u l a t i o n o f a n g i o g e n e s i s a n d m a t r i x r e m o d e l i n g b y l o c a l i z e d , m a t r i x - m e d i a t e d a n t i s e n s e g e n e d e l i v e r y . M o l T h e r 3 : 8 4 2 - 9 ; 2 0 0 1 .
8 6 . A h n , S . H . , K i m , C . S . , S u k , H . J . , L e e , Y . J . , C h o i , S . H . , C h a i , J . K . , i s u r . E f f e c t o f r e c o m b i n a n t h u m a n b o n e m o r p h o g e n e t i c p r o t e i n - 4 w i t h c a r r i e r s i n r a t c a l v a r i a l d e f e c t s . J P e r i o d o n t o l 7 4 : 7 8 7 - 9 7 ; 2 0 0 3 .
8 7 . M e i n e l , L . , H o f m a n n , S . , K a r a g e o r g i o u , V . , K i r k e r - H e a d , C . , M c C o o l , J . , G r o n o w i c z , G . , i s u r . T h e i n f l a m m a t o r y r e s p o n s e s t o s i l k f i l m s i n v i t r o a n d i n v i v o . B i o m a t e r i a l s 2 6 : 1 4 7 - 5 5 ; 2 0 0 5 .
8 8 . P e i s t e r , A . , M e l l a d , J . A . , L a r s o n , B . L . , H a l l , B . M . , G i b s o n , L . F . , P r o c k o p , D . J . A d u l t s t e m c e l l s f r o m b o n e m a r r o w ( M S C s ) i s o l a t e d f r o m d i f f e r e n t s t r a i n s o f i n b r e d m i c e v a r y i n s u r f a c e e p i t o p e s , r a t e s o f p r o l i f e r a t i o n , a n d d i f f e r e n t i a t i o n p o t e n t i a l . B l o o d 1 0 3 : 1 6 6 2 - 8 ; 2 0 0 4 .
8 9 . B i a n c h i , G . , B a n f i , A . , M a s t r o g i a c o m o , M . , N o t a r o , R . , L u z z a t t o , L . , C a n c e d d a , R . , i s u r . E x v i v o e n r i c h m e n t o f m e s e n c h y m a l c e l l p r o g e n i t o r s b y f i b r o b l a s t g r o w t h f a c t o r 2 . E x p C e l l R e s 2 8 7 : 9 8 - 1 0 5 ; 2 0 0 3 .
9 0 . K a l a j z i c , I . , K a l a j z i c , Z . , H u r l e y , M . M . , L i c h t l e r , A . C . , R o w e , D . W . S t a g e s p e c i f i c i n h i b i t i o n o f o s t e o b l a s t l i n e a g e d i f f e r e n t i a t i o n b y F G F 2 a n d n o g g i n . J C e l l B i o c h e m 8 8 : 1 1 6 8 - 7 6 ; 2 0 0 3 .
9 1 . M a r t i n , I . , M u r a g l i a , A . , C a m p a n i l e , G . , C a n c e d d a , R . , Q u a r t o , R . F i b r o b l a s t g r o w t h f a c t o r - 2 s u p p o r t s e x v i v o e x p a n s i o n a n d m a i n t e n a n c e o f o s t e o g e n i c p r e c u r s o r s f r o m h u m a n b o n e m a r r o w . E n d o c r i n o l o g y 1 3 8 : 4 4 5 6 - 6 2 ; 1 9 9 7 .
9 2 . S a h n i , A . , F r a n c i s , C . W . S t i m u l a t i o n o f e n d o t h e l i a l c e l l p r o l i f e r a t i o n b y F G F - 2 i n t h e p r e s e n c e o f f i b r i n o g e n r e q u i r e s a l p h a v b e t a 3 . B l o o d 1 0 4 : 3 6 3 5 - 4 1 ; 2 0 0 4 .
9 3 . C h e n , X . D . , Q i a n , H . Y . , N e f f , L . , S a t o m u r a , K . , H o r o w i t z , M . C . T h y - 1 a n t i g e n e x p r e s s i o n b y c e l l s i n t h e o s t e o b l a s t l i n e a g e . J B o n e M i n e r R e s 1 4 : 3 6 2 - 7 5 ; 1 9 9 9 .
9 4 . G r o n t h o s , S . , Z a n n e t t i n o , A . C . , G r a v e s , S . E . , O h t a , S . , H a y , S . J . , S i m m o n s , P . J . D i f f e r e n t i a l c e l l s u r f a c e e x p r e s s i o n o f t h e S T R O - 1 a n d a l k a l i n e p h o s p h a t a s e a n t i g e n s o n d i s c r e t e d e v e l o p m e n t a l s t a g e s i n p r i m a r y c u l t u r e s o f h u m a n b o n e c e l l s . J B o n e M i n e r R e s 1 4 : 4 7 - 5 6 ; 1 9 9 9 .
9 5 . Z a n n e t t i n o , A . C . , H a r r i s o n , K . , J o y n e r , C . J . , T r i f f i t t , J . T . , S i m m o n s , P . J . M o l e c u l a r c l o n i n g o f t h e c e l l s u r f a c e a n t i g e n i d e n t i f i e d b y t h e o s t e o p r o g e n i t o r - s p e c i f i c m o n o c l o n a l a n t i b o d y , H O P - 2 6 . J C e l l B i o c h e m 8 9 : 5 6 - 6 6 ; 2 0 0 3 .
9 6 . L i u , F . , M a l a v a l , L . , A u b i n , J . E . T h e m a t u r e o s t e o b l a s t p h e n o t y p e i s c h a r a c t e r i z e d b y e x t e n s i v e p l a s t i c i t y . E x p C e l l R e s 2 3 2 : 9 7 - 1 0 5 ; 1 9 9 7 .
9 7 . K a l a j z i c , I . , K a l a j z i c , Z . , K a l i t e r n a , M . , G r o n o w i c z , G . , C l a r k , S . H . , L i c h t l e r , A . C . , i s u r . U s e o f t y p e I c o l l a g e n g r e e n f l u o r e s c e n t p r o t e i n t r a n s g e n e s t o i d e n t i f y s u b p o p u l a t i o n s o f c e l l s a t d i f f e r e n t s t a g e s o f t h e o s t e o b l a s t l i n e a g e . J B o n e M i n e r R e s 1 7 : 1 5 - 2 5 ; 2 0 0 2 .
9 8 . D a c i c , S . , K a l a j z i c , I . , V i s n j i c , D . , L i c h t l e r , A . C . , R o w e , D . W . C o l 1 a 1 - d r i v e n t r a n s g e n i c m a r k e r s o f o s t e o b l a s t l i n e a g e p r o g r e s s i o n . J B o n e M i n e r R e s 1 6 : 1 2 2 8 - 3 6 ; 2 0 0 1 .
9 9 . K a l a j z i c , Z . , L i u , P . , K a l a j z i c , I . , D u , Z . , B r a u t , A . , M i n a , M . , i s u r . D i r e c t i n g t h e e x p r e s s i o n o f a g r e e n f l u o r e s c e n t p r o t e i n t r a n s g e n e i n d i f f e r e n t i a t e d o s t e o b l a s t s : c o m p a r i s o n b e t w e e n r a t t y p e I c o l l a g e n a n d r a t o s t e o c a l c i n p r o m o t e r s . B o n e 3 1 : 6 5 4 - 6 0 ; 2 0 0 2 .
1 0 0 . J i a n g , X . , K a l a j z i c , Z . , M a y e , P . , B r a u t , A . , B e l l i z z i , J . , M i n a , M . , i s u r . H i s t o l o g i c a l a n a l y s i s o f G F P e x p r e s s i o n i n m u r i n e b o n e . J H i s t o c h e m C y t o c h e m 5 3 : 5 9 3 - 6 0 2 ; 2 0 0 5 .
1 0 1 . K e s t e r s o n , R . A . , S t a n l e y , L . , D e M a y o , F . , F i n e g o l d , M . , P i k e , J . W . T h e h u m a n o s t e o c a l c i n p r o m o t e r d i r e c t s b o n e - s p e c i f i c v i t a m i n D - r e g u l a t a b l e g e n e e x p r e s s i o n i n t r a n s g e n i c m i c e . M o l E n d o c r i n o l 7 : 4 6 2 - 7 ; 1 9 9 3 .
1 0 2 . M o r r i s o n , N . A . , S h i n e , J . , F r a g o n a s , J . C . , V e r k e s t , V . , M c M e n e m y , M . L . , E i s m a n , J . A . 1 , 2 5 - d i h y d r o x y v i t a m i n D - r e s p o n s i v e e l e m e n t a n d g l u c o c o r t i c o i d r e p r e s s i o n i n t h e o s t e o c a l c i n g e n e . S c i e n c e 2 4 6 : 1 1 5 8 - 6 1 ; 1 9 8 9 .
1 0 3 . S i m s , N . A . , W h i t e , C . P . , S u n n , K . L . , T h o m a s , G . P . , D r u m m o n d , M . L . , M o r r i s o n , N . A . , i s u r . H u m a n a n d m u r i n e o s t e o c a l c i n g e n e e x p r e s s i o n : c o n s e r v e d t i s s u e r e s t r i c t e d e x p r e s s i o n a n d d i v e r g e n t r e s p o n s e s t o 1 , 2 5 - d i h y d r o x y v i t a m i n D 3 i n v i v o . M o l E n d o c r i n o l 1 1 : 1 6 9 5 - 7 0 8 ; 1 9 9 7 .
1 0 4 . K e r n e r , S . A . , S c o t t , R . A . , P i k e , J . W . S e q u e n c e e l e m e n t s i n t h e h u m a n o s t e o c a l c i n g e n e c o n f e r b a s a l a c t i v a t i o n a n d i n d u c i b l e r e s p o n s e t o h o r m o n a l v i t a m i n D 3 . P r o c N a t l A c a d S c i U S A 8 6 : 4 4 5 5 - 9 ; 1 9 8 9 .
1 0 5 . C l e m e n s , T . L . , T a n g , H . , M a e d a , S . , K e s t e r s o n , R . A . , D e m a y o , F . , P i k e , J . W . , i s u r . A n a l y s i s o f o s t e o c a l c i n e x p r e s s i o n i n t r a n s g e n i c m i c e r e v e a l s a s p e c i e s d i f f e r e n c e i n v i t a m i n D r e g u l a t i o n o f m o u s e a n d h u m a n o s t e o c a l c i n g e n e s . J B o n e M i n e r R e s 1 2 : 1 5 7 0 - 6 ; 1 9 9 7 .
1 0 6 . G r i f f i t h s , J . M . , H J ; S u z u k i , T D ; L e w o n t i n , R C ; G e l b a r t , M W A n I n t r o d u c t i o n t o G e n e t i c A n a l y s i s . N e w Y o r k : W . H . F r e e m a n ; 2 0 0 0 .
1 0 7 . M o t o i k e , T . , L o u g h n a , S . , P e r e n s , E . , R o m a n , B . L . , L i a o , W . , C h a u , T . C . , i s u r . U n i v e r s a l G F P r e p o r t e r f o r t h e s t u d y o f v a s c u l a r d e v e l o p m e n t . G e n e s i s 2 8 : 7 5 - 8 1 ; 2 0 0 0 .
1 0 8 . G e n o v e s e , C . , R o w e , D . , K r e a m , B . C o n s t r u c t i o n o f D N A s e q u e n c e s c o m p l e m e n t a r y t o r a t a l p h a 1 a n d a l p h a 2 c o l l a g e n m R N A a n d t h e i r u s e i n s t u d y i n g t h e r e g u l a t i o n o f t y p e I c o l l a g e n s y n t h e s i s b y 1 , 2 5 - d i h y d r o x y v i t a m i n D . B i o c h e m i s t r y 2 3 : 6 2 1 0 - 6 ; 1 9 8 4 .
1 0 9 . C e l e s t e , A . J . , R o s e n , V . , B u e c k e r , J . L . , K r i z , R . , W a n g , E . A . , W o z n e y , J . M . I s o l a t i o n o f t h e h u m a n g e n e f o r b o n e g l a p r o t e i n u t i l i z i n g m o u s e a n d r a t c D N A c l o n e s . E m b o J 5 : 1 8 8 5 - 9 0 ; 1 9 8 6 .
1 1 0 . Y o u n g , M . F . , I b a r a k i , K . , K e r r , J . M . , L y u , M . S . , K o z a k , C . A . M u r i n e b o n e s i a l o p r o t e i n ( B S P ) : c D N A c l o n i n g , m R N A e x p r e s s i o n , a n d g e n e t i c m a p p i n g . M a m m G e n o m e 5 : 1 0 8 - 1 1 ; 1 9 9 4 .
1 1 1 . B r a u t , A . , K o l l a r , E . J . , M i n a , M . A n a l y s i s o f t h e o d o n t o g e n i c a n d o s t e o g e n i c p o t e n t i a l s o f d e n t a l p u l p i n v i v o u s i n g a C o l 1 a 1 - 2 . 3 - G F P t r a n s g e n e . I n t J D e v B i o l 4 7 : 2 8 1 - 9 2 ; 2 0 0 3 .
1 1 2 . W a n g , Y . H . , L i u , Y . , B u h l , K . , R o w e , D . W . C o m p a r i s o n o f t h e a c t i o n o f t r a n s i e n t a n d c o n t i n u o u s P T H o n p r i m a r y o s t e o b l a s t c u l t u r e s e x p r e s s i n g d i f f e r e n t i a t i o n s t a g e - s p e c i f i c G F P . J B o n e M i n e r R e s 2 0 : 5 - 1 4 ; 2 0 0 5 .
1 1 3 . P o c k w i n s e , S . M . , L a w r e n c e , J . B . , S i n g e r , R . H . , S t e i n , J . L . , L i a n , J . B . , S t e i n , G . S . G e n e e x p r e s s i o n a t s i n g l e c e l l r e s o l u t i o n a s s o c i a t e d w i t h d e v e l o p m e n t o f t h e b o n e c e l l p h e n o t y p e : u l t r a s t r u c t u r a l a n d i n s i t u h y b r i d i z a t i o n a n a l y s i s . B o n e 1 4 : 3 4 7 - 5 2 ; 1 9 9 3 .
1 1 4 . K u z n e t s o v , S . A . , K r e b s b a c h , P . H . , S a t o m u r a , K . , K e r r , J . , R i m i n u c c i , M . , B e n a y a h u , D . , i s u r . S i n g l e - c o l o n y d e r i v e d s t r a i n s o f h u m a n m a r r o w s t r o m a l f i b r o b l a s t s f o r m b o n e a f t e r t r a n s p l a n t a t i o n i n v i v o . J B o n e M i n e r R e s 1 2 : 1 3 3 5 - 4 7 ; 1 9 9 7 .
1 1 5 . H o t t a , T . , M u r a t e , T . , U t s u m i , M . , H i r a b a y a s h i , N . , Y a m a d a , H . O r i g i n s o f h e m o p o i e t i c a n d s t r o m a l c e l l s i n s u b c u t a n e o u s f e m u r i m p l a n t s . E x p H e m a t o l 1 1 : 1 0 7 - 1 3 ; 1 9 8 3 .
1 1 6 . K o n d o , M . , W a g e r s , A . J . , M a n z , M . G . , P r o h a s k a , S . S . , S c h e r e r , D . C . , B e i l h a c k , G . F . , i s u r . B i o l o g y o f h e m a t o p o i e t i c s t e m c e l l s a n d p r o g e n i t o r s : i m p l i c a t i o n s f o r c l i n i c a l a p p l i c a t i o n . A n n u R e v I m m u n o l 2 1 : 7 5 9 - 8 0 6 ; 2 0 0 3 .
1 1 7 . C o t t a , C . V . , Z h a n g , Z . , K i m , H . G . , K l u g , C . A . P a x 5 d e t e r m i n e s B - v e r s u s T - c e l l f a t e a n d d o e s n o t b l o c k e a r l y m y e l o i d - l i n e a g e d e v e l o p m e n t . B l o o d 1 0 1 : 4 3 4 2 - 6 ; 2 0 0 3 .
1 1 8 . K a l a j z i c , I . , S t a a l , A . , Y a n g , W . P . , W u , Y . , J o h n s o n , S . E . , F e y e n , J . H . , i s u r . E x p r e s s i o n p r o f i l e o f o s t e o b l a s t l i n e a g e a t d e f i n e d s t a g e s o f d i f f e r e n t i a t i o n . J B i o l C h e m 2 8 0 : 2 4 6 1 8 - 2 6 ; 2 0 0 5 .
1 1 9 . K a l a j z i c , I . , B r a u t , A . , G u o , D . , J i a n g , X . , K r o n e n b e r g , M . S . , M i n a , M . , i s u r . D e n t i n m a t r i x p r o t e i n 1 e x p r e s s i o n d u r i n g o s t e o b l a s t i c d i f f e r e n t i a t i o n , g e n e r a t i o n o f a n o s t e o c y t e G F P - t r a n s g e n e . B o n e 3 5 : 7 4 - 8 2 ; 2 0 0 4 .
1 2 0 . L i a n , J . B . , M c K e e , M . D . , T o d d , A . M . , G e r s t e n f e l d , L . C . I n d u c t i o n o f b o n e - r e l a t e d p r o t e i n s , o s t e o c a l c i n a n d o s t e o p o n t i n , a n d t h e i r m a t r i x u l t r a s t r u c t u r a l l o c a l i z a t i o n w i t h d e v e l o p m e n t o f c h o n d r o c y t e h y p e r t r o p h y i n v i t r o . J C e l l B i o c h e m 5 2 : 2 0 6 - 1 9 ; 1 9 9 3 .
1 2 1 . Z a g b a - M o n g a l i m a , G . , G o r e t - N i c a i s e , M . , D h e m , A . A g e c h a n g e s i n h u m a n b o n e : a m i c r o r a d i o g r a p h i c a n d h i s t o l o g i c a l s t u d y o f s u b p e r i o s t e a l a n d p e r i o s t e a l c a l c i f i c a t i o n s . G e r o n t o l o g y 3 4 : 2 6 4 - 7 6 ; 1 9 8 8 .
1 2 2 . A l l e n , M . R . , B u r r , D . B . H u m a n f e m o r a l n e c k h a s l e s s c e l l u l a r p e r i o s t e u m , a n d m o r e m i n e r a l i z e d p e r i o s t e u m , t h a n f e m o r a l d i a p h y s e a l b o n e . B o n e 3 6 : 3 1 1 - 6 ; 2 0 0 5 .
1 2 3 . V a j d a , E . G . , B l o e b a u m , R . D . A g e - r e l a t e d h y p e r m i n e r a l i z a t i o n i n t h e f e m a l e p r o x i m a l h u m a n f e m u r . A n a t R e c 2 5 5 : 2 0 2 - 1 1 ; 1 9 9 9 .
1 2 4 . S h e a , J . E . , V a j d a , E . G . , B l o e b a u m , R . D . E v i d e n c e o f a h y p e r m i n e r a l i s e d c a l c i f i e d f i b r o c a r t i l a g e o n t h e h u m a n f e m o r a l n e c k a n d l e s s e r t r o c h a n t e r . J A n a t 1 9 8 : 1 5 3 - 6 2 ; 2 0 0 1 .
1 2 5 . W a n g , L . , L i u , Y . , K a l a j z i c , Z . , J i a n g , X . , R o w e , D . W . H e t e r o g e n e i t y o f e n g r a f t e d b o n e - l i n i n g c e l l s a f t e r s y s t e m i c a n d l o c a l t r a n s p l a n t a t i o n . B l o o d 1 0 6 : 3 6 5 0 - 7 ; 2 0 0 5 .
1 2 6 . A l l o u c h e , M . B a s i c f i b r o b l a s t g r o w t h f a c t o r a n d h e m a t o p o i e s i s . L e u k e m i a 9 : 9 3 7 - 4 2 ; 1 9 9 5 .
1 2 7 . Z h a n g , X . , S o b u e , T . , H u r l e y , M . M . F G F - 2 i n c r e a s e s c o l o n y f o r m a t i o n , P T H r e c e p t o r , a n d I G F - 1 m R N A i n m o u s e m a r r o w s t r o m a l c e l l s . B i o c h e m B i o p h y s R e s C o m m u n 2 9 0 : 5 2 6 - 3 1 ; 2 0 0 2 .
1 2 8 . D o m i n i c i , M . , P r i t c h a r d , C . , G a r l i t s , J . E . , H o f m a n n , T . J . , P e r s o n s , D . A . , H o r w i t z , E . M . H e m a t o p o i e t i c c e l l s a n d o s t e o b l a s t s a r e d e r i v e d f r o m a c o m m o n m a r r o w p r o g e n i t o r a f t e r b o n e m a r r o w t r a n s p l a n t a t i o n . P r o c N a t l A c a d S c i U S A 1 0 1 : 1 1 7 6 1 - 6 ; 2 0 0 4 .
1 2 9 . F r i e d e n s t e i n , A . , K u r a l e s o v a , A . I . O s t e o g e n i c p r e c u r s o r c e l l s o f b o n e m a r r o w i n r a d i a t i o n c h i m e r a s . T r a n s p l a n t a t i o n 1 2 : 9 9 - 1 0 8 ; 1 9 7 1 .
1 3 0 . F r i e d e n s t e i n , A . J . , I v a n o v - S m o l e n s k i , A . A . , C h a j l a k j a n , R . K . , G o r s k a y a , U . F . , K u r a l e s o v a , A . I . , L a t z i n i k , N . W . , i s u r . O r i g i n o f b o n e m a r r o w s t r o m a l m e c h a n o c y t e s i n r a d i o c h i m e r a s a n d h e t e r o t o p i c t r a n s p l a n t s . E x p H e m a t o l 6 : 4 4 0 - 4 ; 1 9 7 8 .
1 3 1 . F r i e d e n s t e i n , A . J . , P e t r a k o v a , K . V . , K u r o l e s o v a , A . I . , F r o l o v a , G . P . H e t e r o t o p i c o f b o n e m a r r o w . A n a l y s i s o f p r e c u r s o r c e l l s f o r o s t e o g e n i c a n d h e m a t o p o i e t i c t i s s u e s . T r a n s p l a n t a t i o n 6 : 2 3 0 - 4 7 ; 1 9 6 8 .
1 3 2 . Q u a n , T . E . , C o w p e r , S . , W u , S . P . , B o c k e n s t e d t , L . K . , B u c a l a , R . C i r c u l a t i n g f i b r o c y t e s : c o l l a g e n - s e c r e t i n g c e l l s o f t h e p e r i p h e r a l b l o o d . I n t J B i o c h e m C e l l B i o l 3 6 : 5 9 8 - 6 0 6 ; 2 0 0 4 .
1 3 3 . B u c a l a , R . , S p i e g e l , L . A . , C h e s n e y , J . , H o g a n , M . , C e r a m i , A . C i r c u l a t i n g f i b r o c y t e s d e f i n e a n e w l e u k o c y t e s u b p o p u l a t i o n t h a t m e d i a t e s t i s s u e r e p a i r . M o l M e d 1 : 7 1 - 8 1 ; 1 9 9 4 .
1 3 4 . Z h a n g , Y . , A d a c h i , Y . , S u z u k i , Y . , M i n a m i n o , K . , I w a s a k i , M . , H i s h a , H . , i s u r . S i m u l t a n e o u s i n j e c t i o n o f b o n e m a r r o w c e l l s a n d s t r o m a l c e l l s i n t o b o n e m a r r o w a c c e l e r a t e s h e m a t o p o i e s i s i n v i v o . S t e m C e l l s 2 2 : 1 2 5 6 - 6 2 ; 2 0 0 4 .
1 3 5 . B o b a n , I . , J a c q u i n , C . , P r i o r , K . , B a r i s i c - D u j m o v i c , T . , M a y e , P . , C l a r k , S . H . , i s u r . T h e 3 . 6 k b D N A f r a g m e n t f r o m t h e r a t C o l 1 a 1 g e n e p r o m o t e r d r i v e s t h e e x p r e s s i o n o f g e n e s i n b o t h o s t e o b l a s t a n d o s t e o c l a s t l i n e a g e c e l l s . B o n e ; 2 0 0 6 .
1 3 6 . P a s s e g u e , E . , J a m i e s o n , C . H . , A i l l e s , L . E . , W e i s s m a n , I . L . N o r m a l a n d l e u k e m i c h e m a t o p o i e s i s : a r e l e u k e m i a s a s t e m c e l l d i s o r d e r o r a r e a c q u i s i t i o n o f s t e m c e l l c h a r a c t e r i s t i c s ? P r o c N a t l A c a d S c i U S A 1 0 0 S u p p l 1 : 1 1 8 4 2 - 9 ; 2 0 0 3 .
1 3 7 . N i s h i m u r a , J . , W a r e , R . E . , B u r n e t t e , A . , P e n d l e t o n , A . L . , K i t a n o , K . , H i r o t a , T . , i s u r . T h e h e m a t o p o i e t i c d e f e c t i n P N H i s n o t d u e t o d e f e c t i v e s t r o m a , b u t i s d u e t o d e f e c t i v e p r o g e n i t o r c e l l s . B l o o d C e l l s M o l D i s 2 9 : 1 5 9 - 6 7 ; 2 0 0 2 .
1 3 8 . L i , X . , P l e t t , P . A . , Y a n g , Y . , H o n g , P . , F r e i e , B . , S r o u r , E . F . , i s u r . F a n c o n i a n e m i a t y p e C - d e f i c i e n t h e m a t o p o i e t i c s t e m / p r o g e n i t o r c e l l s e x h i b i t a b e r r a n t c e l l c y c l e c o n t r o l . B l o o d 1 0 2 : 2 0 8 1 - 4 ; 2 0 0 3 .
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