细胞因子periostin在肌腱粘连中的作用及分子机制研究

Peritendinous fibrosis, a common disorder in the orthopaedic field, is at a high incidence after tendon injury. Peritendinous fibrosis seriously impairs limb function and affects the quality of life. Our previous studies showed that periostin expression was significantly up-regulated in rats and patients with peritendinous fibrosis. Then we overexpressed periostin by adeno-associated virus in primary tenocytes, and found that cell proliferation, activity, and production of extracellular matrix (ECM) were significantly up-regulated by periostin. Meanwhile, JNK signaling pathway was also significantly activated. The above results suggest that aberrant expression of periostin may be involved in the development of Peritendinous fibrosis after tendon injury. Based on these important findings, we will further focus on the role and mechanism of periostin in peritendinous fibrosis: 1) to clarify the biological function of periostin on cell proliferation, apoptosis, cell cycle, and ECM production; 2) to clarify the molecular mechanism of periostin. Our study will not only help to reveal the pathogenesis of peritendinous fibrosis, but also provide a new theoretical basis and therapeutic strategy.

肌腱粘连是骨科常见的疾病，在肌腱损伤后发生率高，严重影响肢体功能和生活质量，目前临床尚缺乏有效的治疗手段。本课题组前期研究发现：肌腱粘连患者和大鼠的病变组织中，periostin的表达显著上调。利用腺相关病毒体外过表达periostin，可促进肌腱细胞的增殖、活化，并显著上调胶原等细胞外基质的合成，同时JNK信号通路显著激活。以上结果提示，肌腱损伤后，periostin可能通过调控JNK信号通路进而参与肌腱粘连的发生发展。本项目拟在前期研究结果的基础上，进一步探索开展一下研究：1）明确periostin对肌腱细胞增殖、细胞外基质合成的调控作用；2）阐明periostin发挥作用的分子机制。本课题的开展，将不仅有助于揭示肌腱粘连的发病机制，也将为防治肌腱粘连提供新的理论依据与策略。

肌腱粘连是骨科常见的疾病，在肌腱损伤后发生率高，严重影响肢体功能和生活质量，目前临床尚缺乏有效的治疗手段。本课题组通过采集肌腱粘连患者和大鼠的病变组织，进行RNA测序，筛选可能参与肌腱粘连发生的相关基因，以及异常的信号通路。通过测序发现periostin的表达显著上调。进一步利用腺相关病毒体外过表达或干扰periostin，可调节肌腱细胞的增殖、活化，以及胶原等细胞外基质的合成，同时JNK信号通路显著激活或抑制。以上结果提示，肌腱损伤后，periostin可能通过调控JNK信号通路进而参与肌腱粘连的发生发展。