BMP‐2 mediates PGE₂‐induced reduction of proliferation and osteogenic differentiation of human tendon stem cells

Tendon stem cells (TSCs) have been proposed to play a major role in the development of tendinopathy, which refers to pathological changes, such as calcification, in affected tendons. Using a human TSC (hTSC) culture model, this study investigated the effects of PGE(2) , an inflammatory mediator present in injured tendons, on hTSC proliferation and differentiation as well as the molecular mediator for such PGE(2) -induced effects. We found that PGE(2) treatment of hTSCs decreased cell proliferation and caused osteogenic differentiation of hTSCs in a dose-dependent manner. Also, PGE(2) treatment of hTSCs induced dose-dependent BMP-2 production in culture, and moreover, addition of BMP-2 to hTSC culture decreased cell proliferation and induced hTSC differentiation into osteoblasts. Finally, addition of BMP-2 antibodies to hTSC culture treated with PGE(2) nearly abolished PGE(2) effects on both cell proliferation and osteogenic differentiation. Taken together, the findings of this study showed that BMP-2 mediates PGE(2) -induced reduction of proliferation and osteogenic differentiation of hTSCs. We suggest that such a mechanism may be partially responsible for the formation of calcified tissues in tendinopathic tendons seen in clinical settings.