title: BMP-2 mediates PGE(2) -induced reduction of proliferation and osteogenic differentiation of human tendon stem cells.
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) -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.
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.forename: James H-C
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000328:Adult; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D017847:Patellar Ligament / Q000166:cytology* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D052256:Tendinopathy / Q000378:metabolism / Q000473:pathology
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D015232:Dinoprostone