软骨细胞微环境变化对软骨损伤修复影响的研究

项目名称： 软骨细胞微环境变化对软骨损伤修复影响的研究

项目编号： No.81330040

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 敖英芳

作者单位： 北京大学

项目金额： 290万元

中文摘要： 关节软骨损伤是难治性损伤，总体发生率在61%以上，常引起关节肿痛等症状，可继发骨关节炎，对普通人群的工作、生活以及运动员运动生涯造成损害，甚至致残。目前尚无理想治疗方法。现有修复方法主要存在两方面问题：一方面缺损区域缺乏有生物活性的成分（细胞，支架）填充。另一方面，这些修复组织缺乏有效的诱导难以分化为软骨细胞或软骨组织。简言之，没有提供给一个与软骨组织相似或相近的特异性微环境。本课题以软骨损伤后的微环境变化为切入点，结合前期结果，一方面研究软骨损伤后损伤区域骨髓间充质干细胞与软骨细胞的相互作用。另一方面研究在软骨损伤修复过程中，是否有相关miRNA和lncRNA参与软骨损伤的过程以及是否参与调控骨髓间充质干细胞分化为软骨细胞，进一步研究其功能。通过这些研究为微环境对软骨细胞的影响提供理论依据，同时筛选软骨损伤修复过程中的关键分子，为进一步用于软骨损伤修复的预防及治疗提供理论及实践依据。

中文关键词： 软骨损伤;软骨修复;微环境;骨髓间充质干细胞;非编码RNA

英文摘要： Articular cartilage injury is the high incidence of refractory disease; the overall incidence is more than 61%. It often gives rise to many symptoms such as joint swelling and pain, leading to the occurrence of osteoarthritis. Thereby, it often affects people's daily life and work. To athletes, it will seriously obstruct their athletic career. Sometime, it can even lead to disability. Now, there still hasn't an effient treatment to solve this problem in worldwide. The existing repair methods exist main problems composed of two aspects: on the one hand, the defect area lacks the biological activity of the component (cells, scaffold) filling, always the scar tissue or fibrous tissue. On the other hand, It’s hard of these repairs tissue to differentiate into chondrocytes or cartilage tissue because of the lack of an effective induction. In a word, there is no similar microenvironment of cartilagethe according to existing treatments on cartilage repair. To solve these problems, the present study was based on the microenvironment changes in cartilage injury. There are two aspects to be investigate in the present study based on preliminary results of our studies: on the one hand, we will investigate the interaction between bone marrow mesenchymal stem cells which recruited after cartilage damage and chondrocytes of cartilage damage, including the suitable amount of bone marrow mesenchymal stem cells raised from bone marrow and whether raising the mesenchymal stem cells are able to promote the repair of cartilage damage. On the other hand, we will research the related miRNA and lncRNA of cartilage damage cartilage injury and repair, as well as whether these factors participated in the cartilage injury and repair and the regulation of bone marrow mesenchymal stem cells into cartilage cells, further study its function. Through these studies, we hope to able to provide a theoretical basis for the influence of microenvironment on chondrocytes. We hope we can screen some key molecules in the cartilage injury and repair process, this not only provide the basis of the theory but also the practice in further used for the prevention and treatment of cartilage damage.

英文关键词： cartilage injury;cartilage regeneration;microenvironment;mesenchymal stem cell;non-coding RNA