Absence of estrogen receptor beta leads to abnormal adipogenesis during early tendon healing by an up-regulation of PPARγ signalling

Achilles tendon injury is one of the challenges of sports medicine, the aetiology of which remains unknown. For a long time, estrogen receptor beta (ER beta) has been known as a regulating factor of the metabolism in many connective tissues, such as bone, muscle and cartilage, but little is known about its role in tendon. Recent studies have implicated ER beta as involved in the process of tendon healing. Tendon-derived stem cells (TDSCs) are getting more and more attention in tendon physiological and pathological process. In this study, we investigated how ER beta played a role in Achilles tendon healing. Achilles tendon injury model was established to analyse how ER beta affected on healing process in vivo. Cell proliferation assay, Western blots, qRT-PCR and immunocytochemistry were performed to investigate the effect of ER beta on TDSCs. Here, we showed that ER beta deletion in mice resulted in inferior gross appearance, histological scores and, most importantly, increased accumulation of adipocytes during the early tendon healing which involved activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) signalling. Furthermore, in vitro results of ours confirmed that the abnormity might be the result of abnormal TDSC adipogenic differentiation which could be partially reversed by the treatment of ER beta agonist LY3201. These data revealed a role of ER beta in Achilles tendon healing for the first time, thereby providing a new target for clinical treatment of Achilles tendon injury.