视黄酸受体γ激动剂在促进肌腱修复及抑制肌腱钙化中的作用

肌腱损伤在日常生活及运动领域十分常见, 损伤后肌腱缺乏有效的修复能力，仅通过瘢痕愈合, 常导致功能障碍和活动受限，且易发生再断裂。此外，肌腱损伤发生后，肌腱钙化为另一种常见且严重的并发症。目前临床中尚无明确的能够促进肌腱自然愈合并抑制肌腱钙化的药物。最近，我们从小鼠及人的损伤肌腱中分离出一种具有干细胞特征的细胞群，并命名为损伤源性肌腱祖细胞。体内细胞示踪实验发现损伤源性肌腱祖细胞同时参与到肌腱修复及钙化过程。体外实验中我们发现视黄酸受体γ激动剂可以促进损伤源性肌腱祖细胞Scx及Tnmd等腱性分化标志物的表达；并抑制Agg及ColⅡ等软骨分化标志物的表达。基于上述预实验结果，我们提出以下假说：视黄酸受体γ激动剂可以促进肌腱损伤后的修复并抑制肌腱钙化。本研究将从体内及体外两个层面来验证视黄酸受体γ激动剂促进肌腱修复并抑制肌腱钙化的有效性及安全性，并探索其作用机制，为寻找新的治疗靶点奠定基础。

Tendon injuries are common in both the workplace and sports activities. Tendons have limited repair capacity. Damaged tendons do not usually regain their original levels of biological and biomechanical characteristics and degeneration of tendon can be highly debilitating and can result in disability, limitation of movement and tendon calcification. There is no effective drug for tendon repair and inhibition of tendon calcification. Recently we reported that injured tendon-derived progenitor cells (inTPCs) rapidly appear and are expanded in mouse and human injured tendons. These cells have characteristics as tendon progenitor cells and are integrated into regenerating tendon. On the other hand, they exhibit stronger spontaneous chondrogenic ability than the normal tendon progenitor cells and are integrated into heterotopic cartilaginous lesion induced in injured tendon. Interestingly, we found that retinoic acid receptor-γ (RAR-γ) agonist stimulate Scx and Tnmd, two tenogenic differentiation marker, expression on inTPCs. And in chondrogenic culture system, RAR-γagonist inhibited Agg and ColⅡ, two chondrogenic differentiation marker, expression on inTPCs. Base on these preliminary results we hypothesize that RAR-γagonist can stimulate tendon repair and inhibit tendon calcification. In this project, we will demonstrate the effectivity and safety of RAR-γagonist in tendon repair and inhibition of tendon calcification. Further more, to explore new therapeutic target for tendon injury we will investigate the mechanism that how RAR-γagonist play the role.