engleski

Osteoclastogenic and osteoblastogenic potential of hematopoietic/stromal cells in collagen induced arthritis

Collagen induced arthritis (CIA) is a mouse model for human rheumatoid arthritis (RA). Our aim was to show the osteoclastogenic potential of bone marrow- and peripheral-hematopoietic cells, and osteoblastogenic potential of bone marrow-derived stromal cells in RA. C57BL/6 mice were immunized with chicken type II collagen (CII) emulsified in complete Freund's adjuvant (FA) and clinically scored for up to 100 days. Circulating levels of anti-CII antibodies IgG1/IgG2a were determined by ELISA. Hematopoietic cells from different cellular sources were cultured with RANKL and M-CSF to stimulate osteoclast (OCL) differentiation. Osteoblast (OB) differentiation was assessed by the number of AP-positive osteoblastogenic colonies and AP activity in cell lysates. Combination of hematopoietic markers were used to characterize population of osteoclast progenitors by flow cytometry. Gene expression analysis for inflammatory and specific genes was performed by qPCR. Our results s! howed that both osteclastogenesis and osteoblastogenesis from hematopoietic/stromal cells are enhanced in CIA. Peripheral-hematopoietic cells but not the bone marrow-hematopoietic cells of mice with CIA contain approximately 2-times more OCL progenitors defined as either CD3-B220-NK1.1-CD11b+CD115+ or CD3-B220-NK1.1-CD11b-CD115+ population. Expression of specific genes confirmed enhanced osteoclastogenic and osteoblastogenic potential of hematopoietic/stromal cells in CIA. Also, expression of inflammatory and bone-resorbing cytokines was enhanced in CIA. Our results indicate that mice with CIA have higher number of OCL progenitors within peripheral hematopoietic cells and greater osteoclastogenic potential compared with control mice, in parallel to enhanced osteoblastogenic potential of bone-marrow cells. Gene expression in hematopoietic and bone tissues further support our hypothesis that chronic inflammation in CIA affect bone metabolism to enhance osteoclastogenesis and osteoblastogenesis.

osteoclasts; osteoblasts; collagen induced arthritis; osteoclast progenitors

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