CRABP2在牵张应力促肌腱干细胞腱系分化中的作用和机制研究

项目名称： CRABP2在牵张应力促肌腱干细胞腱系分化中的作用和机制研究

项目编号： No.81501606

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 徐源

作者单位： 中国人民解放军第三军医大学

项目金额： 18万元

中文摘要： 牵张应力刺激促进肌腱干细胞（TSCs）腱系分化，明显提高TSCs-支架复合物生物学活性，利于损伤肌腱再生修复，故研究牵张应力刺激促进TSCs腱系分化的机制非常重要。前期研究证实，牵张应力刺激促进TSCs腱系分化时明显上调细胞视黄酸结合蛋白2（CRABP2）表达，鉴于CRABP2是视黄酸信号通路的重要组成部分，对多种细胞具有诱导分化作用，因此，本项目着力于验证CRABP2表达对TSCs腱系分化的影响，并阐明牵张应力刺激对其激活的分子机制。拟在牵张应力刺激下培养以TSCs构建的组织工程肌腱，观察条件性沉默或增强CRABP2表达对TSCs增殖、腱系分化表型的影响，通过离体、在体实验揭示CRABP2在牵张应力促进损伤肌腱修复中的作用；并通过抑制ERK/SP1及Rac1/NF-kB信号通路实验，进一步揭示牵张应力刺激激活CRABP2表达的可能机制，为开发促进肌腱损伤修复的生物治疗新措施提供实验依据。

中文关键词： 牵张应力；CRABP2；；肌腱干细胞；腱系分化

英文摘要： Cyclic tensile strain induces tenogenic differentiation of tendon-derived stem cells (TDSCs), and dynamically cultured TDSCs-scaffold construct could significantly contributed to tendon regeneration, so, the important thing is to find out the mechanism that cyclic tensile strain promoted tenogenic differentiation of TSCs. In our previous work, we confirmed that cyclic ensile strain were significantly unregulated retinoic acid binding protein 2 (CRABP2) expression in TSCs in the above process. CRABP2 is an important part of the retinoic acid signaling pathway which closely associated with cell differentiation. Therefore, this project focused on the effects of CRABP2 expression for tenogenic differentiation of TSCs, and the mechanisms of cyclic tensile strain activate the CRABP2 expression in TSCs. This study aimed to investigate the proliferation and tenogenic differentiation of TSCs induced by cyclic tensile strain, when CRABP2 expression were suppressed or enhanced conditional. The experiments in vitro and in vivo were also designed to investigate the effect of CRABP2 in the course of cyclic tensile strain promoting tendon healing. And experiments that inhibition of ERK/SP1 and Rac1/NF-kB signal ways were designed to further reveal the possible mechanisms of cyclic tensile strain upregulates CRABP2 expression. These results provide an experimental basis for the development of new biological treatments to help promote tendon healing after injury.

英文关键词： Cyclic tensile strain;CRABP2;Tendon stem cells;Tenogenic differentiation