胸腺素β4对肌腱干细胞生物学特性的调控作用及其促进肌腱优质愈合的分子机制

项目名称： 胸腺素β4对肌腱干细胞生物学特性的调控作用及其促进肌腱优质愈合的分子机制

项目编号： No.81472085

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 姜大朋

作者单位： 上海交通大学

项目金额： 72万元

中文摘要： 肌腱损伤后愈合速度慢，并且常呈瘢痕性愈合，其生物学特性显著差于正常肌腱，严重影响功能。胸腺素β4（thymosin β4,Tβ4）是具有促细胞增殖分化、迁移及促进基质重塑等多种生物学功能的G-肌动蛋白结合肽。我们前期研究结果表明：Tβ4可以加快肌腱愈合速度并且使愈合后肌腱胶原纤维排列更为规则。本课题设想Tβ4可以通过调控肌腱干细胞生物学特性促进肌腱修复，另外，Tβ4对愈合过程中肌成纤维细胞转分化以及MMP/TIMP系统平衡表达可能亦具有调节作用，进而达到优质愈合。本课题以Tβ4是否通过调控上述机制来优化肌腱愈合以及其是否通过干扰Rho／ROCK信号转导通路发挥作用为切入点，拟利用大鼠肌腱干细胞、成纤维细胞体外培养及髌腱急性损伤动物模型，探索Tβ4在组织学、生物化学及生物力学等方面优化肌腱愈合的内在分子机制，本研究的成功实施将为提高肌腱愈合质量提供新的治疗策略和理论依据。

中文关键词： 胸腺素β4；肌腱干细胞；成纤维细胞；肌腱；细胞外基质

英文摘要： Tendon heals slowly by scar formation after injury. The biological properties of healing tissue are inferior to the normal tendon tissue, which lead to impairment of function. Thymosin β4 (Tβ4) is mainly recognized as a regulator of actin polymerization by sequestering G-actin. Recent studies have demonstrated that Tβ4 is a multifunctional peptide. It promotes a variety of physiological functions such as proliferation, chemotaxis, tissue repair, and tissue remodeling. We found that the administration of Tβ4 accelerated tendon healing and improved the organization of collagen fibers in the repair site of tendon tissue. In the present research, we hypotheses that Tβ4 could optimize the repair of injured tendon by regulating tendon stem cells. Moreover, Tβ4 may play important role in the restoration of structure and function after tendon injury by modulating myofibroblast differentiation and the balance of MMP/TIMP system during tendon healing process, which result in optimized regeneration. We hypotheses that Tβ4 optimize the regeneration of injured tendon by regulating above mentioned mechanisms and interfering with Rho/ROCK signal pathway, which served as the breakthrough point in this study. We will further explore the underlying molecular mechanism of Tβ4 improving the histological, biochemical and biomechanical properties of the healing tendon in this study. Tendon stem cells and fibroblasts cultured in vitro and the animal model of patellar tendon injury were used in the experiment. The result of this research may provide a new treatment strategy and theoretical basis for improving the quality of the healing tendon tissue.

英文关键词： thymosin β4;tendon stem cell;fibroblast;tendon;extracellular matrix