Abstract
Achilles tendon injury is one of the challenges of sports medicine, the aetiology of which remains unknown. For a long time, estrogen receptor β (ERβ) 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 ERβ 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 ERβ played a role in Achilles tendon healing. Achilles tendon injury model was established to analyse how ERβ affected on healing process in vivo. Cell proliferation assay, Western blots, qRT‐PCR and immunocytochemistry were performed to investigate the effect of ERβ on TDSCs. Here, we showed that ERβ 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 γ (PPARγ) 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 ERβ agonist LY3201. These data revealed a role of ERβ in Achilles tendon healing for the first time, thereby providing a new target for clinical treatment of Achilles tendon injury.
Highlights
Injury owing to sports has risen with the sports participation being increasingly popular in recent years, among which the Achilles ten‐ don injury has been one of the most common
| 7407 in mice led to abnormal adipocyte accumulation via up‐regulation of expression of peroxisome proliferator‐activated receptor γ (PPARγ) signalling which might be related to Tendon‐derived stem cells (TDSCs) adipogenesis that could be partially attenuated by LY3201
Genes related to adipogenic differentiation, PPARγ and FABP4, presented the same characteristics (Figure 4R,S). These results showed that activation of estrogen receptor β (ERβ) by LY3201 promoted the proliferative capacity and inhib‐ ited the adipogenic differentiation of TDSCs, and this kind of ef‐ fect was dose‐dependent
Summary
Injury owing to sports has risen with the sports participation being increasingly popular in recent years, among which the Achilles ten‐ don injury has been one of the most common. According to our clinical observations and statistical data, one of the possible intrinsic factors that predispose athletes to Achilles tendon rupture is the level of oestrogen.[3]. A systematic review on pre‐ and post‐menopausal women showed that the effect of oestrogen supplementation on tendon was contradictory and inconsistent. Modulation of ERβ has raised more attention, due to its promising role in more applications,[15] such as some types of cancer and neuropathies, and because it has less side effects compared to activating estrogen receptor α (ERα). As for tendon healing, one study on rat Achilles tendon showed that oestrogen has a positive effect.[6]. We found that ERβ played an important role in the healing process of tendon injury. | 7407 in mice led to abnormal adipocyte accumulation via up‐regulation of expression of PPARγ signalling which might be related to TDSC adipogenesis that could be partially attenuated by LY3201
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