力学刺激通过整合素α5β1介导的细胞凋亡途径促进半月板退行性变

项目名称： 力学刺激通过整合素α5β1介导的细胞凋亡途径促进半月板退行性变

项目编号： No.81501904

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： 张洋

作者单位： 南方医科大学

项目金额： 18万元

中文摘要： 半月板是维持膝关节正常生理功能的重要结构，许多膝关节疾病常以半月板退变为初始病理改变。力学刺激对半月板纤维软骨的增殖和分化十分重要，但过度的力学刺激可能会导致半月板退变。有研究表明，整合素家族在人体承力组织的力—化学转导中扮演重要角色，其中整合素α5β1的响应可能与退行性变有关；且整合素α5β1可通过粘着斑激酶相关途径抑制细胞凋亡。但目前为止关于半月板的力学响应和退变机制仍不清楚，整合素α5β1所扮演的角色也未知。我们的前期研究表明，不同退变程度的半月板中整合素α5β1的表达有显著差异：退变程度越严重，整合素α5β1的表达越低，同时PI3K的表达也越低。由此我们提出假设，力学刺激通过整合素α5β1介导的细胞凋亡途径促进半月板退变。进一步研究中我们将通过siRNA、qRT-PCR、流式细胞仪等方法验证上述假说，其结果将对半月板疾病的临床诊治和组织工程起到推进作用。

中文关键词： 半月板；整合素；退行性变；力学刺激

英文摘要： Meniscus is regarded as the important structure for alignment of the knee joint, which could reduce the abrasion of articular cartilage. Mechanical stimulation plays a key role in the proliferation and differentiation of fibrochondrocyte of meniscus. It has been proved that the combination of integrin and extracellular matrix would lead to the biochemical response to mechanical stimulation. The expression of integrin α5β1 has been found in human meniscus, however, the existing studies could not tell, that in human meniscus, the exact response of integrin to mechanical stimulation and its influence on fibrochondrocyte. In our previous research, cell culture of human meniscus fibrochondrocyte had been accomplished, and the difference of integrin α5β1 expression was proved: integrin α5β1 espressed lower in meniscus of more serious degeneration, so did the expression of PI3K. Thus it was hypothesised that nechanical stimulation led to meniscus degeneration through cell apoptosis mediated by integrin α5β1.The current study aims to investigate the influence of hydrostatic pressure and shear force on fibrochondrocyte via integrin signal pathways. The results would promote the treatment of cartilage injury and degenerative disease, cartilage tissue engineering, and medical materials.

英文关键词： Meniscus;Integrin;Degenerative disease;Mechanical stimulation