Abstract
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~โinduced effects. We found that PGE~2~ treatment of hTSCs decreased cell proliferation and caused osteogenic differentiation of hTSCs in a doseโdependent manner. Also, PGE~2~ treatment of hTSCs induced doseโdependent BMPโ2 production in culture, and moreover, addition of BMPโ2 to hTSC culture decreased cell proliferation and induced hTSC differentiation into osteoblasts. Finally, addition of BMPโ2 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 BMPโ2 mediates PGE~2~โinduced 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. ยฉ 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:47โ52, 2012