治疗腱损伤的关键在于重建腱止点梯度（肌腱、软骨与骨组成的平滑过渡），但腱止点梯度形成机制尚不明了。前期研究发现腱止点从肌腱端到骨端存在着转化生长因子影响因子1(Tgif1)从多到少的分布规律，预实验提示Tgif1可能能通过调控Smad2来介导肌腱与软骨细胞的相互转化，同时前期研究表明肌腱干细胞能促进腱止点梯度的修复。因此我们假设：Tgif1基因能通过调节Smad2来调控肌腱与软骨的相互转化，从而促进腱止点生理梯度的形成与修复。我们拟通过四步实验，来验证假说：一、通过基因修饰技术观察Tgif1表达对不同细胞细胞表型的影响；二、采用双荧光素酶检测、免疫共沉淀技术研究Tgif1对Smad2的调控机制；三、通过基因修饰技术研究肌腱干细胞促修复原理；四、应用组织工程学技术探讨人工模拟Tgif1梯度治疗腱损伤的可行性。本研究对阐明腱止点梯度形成机制、探索腱损伤治疗方法有重要作用。

The key point for the treatment of tendon injuries is to reconstruct the gradation structure of the tendon to bone interface: smooth transformation consist of tendon, fibrocartilage, and bone. We found there's a gradation of the volume of Tgif1 in the tendon enthesis according to the proteomics. And Tgif1 was able to regulate the transformation between tenocytes and chondrocytes by modifying Smad2. Additionally, tendon derived stem cells were found to be able to regenerate the gradation structure. We hypothese the gradation of Tgif1 results to the formation and regeneration of the gradation structure of the tendon enthesis. We propose to explore the effect of Tgif1 on various cells firstly; then investigate the mechanism of the regulation of Tgif1 to Smad2; next we will explore the role of Tgif1 in the regeneration of tendon bone insertion induced by TDSCs; finally, mimesis the expression pattern of the nature tendon enthesis in TDSCs and investigate its effect in tendon enthesis regeneration. With the help of this study, we can explain the mechanism of the formation of the tendon enthesis. Consequently, explore a new way for the repair of the tendon enthesis.