Prostaglandin E2 (PGE2) exerts biphasic effects on human tendon stem cells.

Prostaglandin E2 (PGE2) 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 PGE2 on human tendon stem/progenitor cells (hTSCs). After treatment with PGE2, hTSC proliferation, stemness, and differentiation were analyzed. We found that high concentrations of PGE2 (>1 ng/ml) decreased cell proliferation and induced non-tenocyte differentiation. However, at lower concentrations (<1 ng/ml), PGE2 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 PGE2 than in cells treated with high levels of PGE2. Moreover, high levels of PGE2 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 PGE2 at concentrations >1 ng/ml. The findings of this study reveal that PGE2 can exhibit biphasic effects on hTSCs, indicating that while high PGE2 concentrations may be detrimental to tendons, low levels of PGE2 may play a vital role in the maintenance of tendon homeostasis in vivo.