Pea3/Scx调控间充质干细胞促进骨-肌腱结合部愈合的机制研究

骨-肌腱结合部（BTJ）损伤修复后以瘢痕连接愈合，难以恢复原本的纤维软骨性结构，再损伤率高。转录因子Scx对肌腱的发育、分化有着至关重要的作用，然而Scx表达的调控机制尚不清楚。我们前期研究显示：在肩袖损伤修复模型中多瘤病毒增强子激活剂3（Pea3）和Scx的表达具有协同性，干扰Pea3的表达后Scx的表达也明显降低。因此我们推测，Pea3可通过调控Scx促进间充质干细胞（MSCs）分化发育，从而促进腱骨愈合。本项目拟深入探索Pea3通过Scx介导促进MSCs分化的作用及机制：细胞水平研究Pea3对Scx表达的作用及对MSCs分化发育的调控；体内实验验证Pea3对BTJ分化发育的影响；并采用肩袖损伤修复动物模型探讨Pea3调控MSCs分化，促进BTJ再生的可行性。本研究将揭示Pea3/Scx的表达在BTJ损伤愈合过程中的作用和机制，为调控干细胞分化而促进BTJ的愈合提供理论依据和潜在方案。

The scar healing is the main way for repair after bone tendon junction (BTJ) injury. Therefore, it is difficult to restore the original fiber cartilage structure and the rate for injury again is relatively high. As one of well recognized tendon specific markers, scleraxis (Scx) has a critical role on differentiation and development of tendon. However, the mechanism on regulation of Scx expression remains poorly unknown. Our previous study demonstrated that both Pea3 and Scx were up-regulated in the model of rotator cuff injury repair. Moreover, scx expression was attenuated after interfering with Pea3 expression. Accordingly, We hypothesize that Pea3 can promote the differentiation and development of MSCs through regulating Scx, thereby benefiting for the repair of rotator cuff injury. This study aims to explore the effect and potential mechanisms of Pea3 in promoting MSCs differentiation and development by modulating Scx. The study mainly include the following parts: 1) detailed mechanism for Pea3 promoting differentiation and development of MSC mediated by Scx in the cellular level; 2) confirmation of the effects for Pea3 on the differentiation and development of BTJ by in vivo experiments; 3) discussion of feasibility and application of Pea3 on BTJ regeneration in a rat model of shoulder cuff injury. Thus, our study will further uncover the mechanism for the expression of Pea3/Scx on the regeneration of BTJ , finally resulting in substantial survival benefit.