An EP2 receptor-selective prostaglandin E2 agonist induces bone healing (CROSBI ID 101137)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Paralkar, V.M. ; Borovečki, Fran ; Ke, H.Z. ; Cameron, K.O. ; Lefker, B. ; Grasser W.A. ; Owen, T.A. ; Li, M. ; DaSilva-Jardine, P. ; Zhou, M. ; Dunn, R.L. ; Dumont, F. ; Korsmeyer, R. ; Krasney, P. ; Brown, T.A. ; Plowchalk, D. ; Vukičević, Slobodan ; Thompson, D.D.
engleski
An EP2 receptor-selective prostaglandin E2 agonist induces bone healing
The morbidity and mortality associated with impaired/delayed fracture healing remain high. Our objective was to identify a small nonpeptidyl molecule with the ability to promote fracture healing and prevent malunions. Prostaglandin E2 (PGE2) causes significant increases in bone mass and bone strength when administered systemically or locally to the skeleton. However, due to side effects, PGE2 is an unacceptable therapeutic option for fracture healing. PGE2 mediates its tissue-specific pharmacological activity via four different G protein-coupled receptor subtypes, EP1, -2, -3, and -4. The anabolic action of PGE2 in bone has been linked to an elevated level of cAMP, thereby implicating the EP2 and/or EP4 receptor subtypes in bone formation. We identified an EP2 selective agonist, CP-533, 536, which has the ability to heal canine long bone segmental and fracture model defects without the objectionable side effects of PGE2, suggesting that the EP2 receptor subtype is a major contributor to PGE2's local bone anabolic activity. The potent bone anabolic activity of CP-533, 536 offers a therapeutic alternative for the treatment of fractures and bone defects in patients.
PGE2; EP2 receptor selective agonist; long bone segmental defect
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Podaci o izdanju
100 (11)
2003.
6736-40.-x
objavljeno
0027-8424