Prostaglandin E(2) (PGE(2)) Exerts Biphasic Effects on Human Tendon Stem Cells

Prostaglandin E(2) (PGE(2)) has been reported to exert different effects on tissues at low and high levels. In the present study, cell culture experiments were performed to determine the potential biphasic effects of PGE(2) on human tendon stem/progenitor cells (hTSCs). After treatment with PGE(2), hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE(2) (>1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (<1 ng/ml), PGE(2) markedly enhanced hTSC proliferation. The expression levels of stem cell marker genes, specifically SSEA-4 and Stro-1, were more extensive in hTSCs treated with low concentrations of PGE(2) than in cells treated with high levels of PGE(2). Moreover, high levels of PGE(2) induced hTSCs to differentiate aberrantly into non-tenocytes, which was evident by the high levels of PPARγ, collagen type II, and osteocalcin expression in hTSCs treated with PGE(2) at concentrations >1 ng/ml. The findings of this study reveal that PGE(2) can exhibit biphasic effects on hTSCs, indicating that while high PGE(2) concentrations may be detrimental to tendons, low levels of PGE(2) may play a vital role in the maintenance of tendon homeostasis in vivo.