创伤性骨关节炎微应力突变机理的探讨

Post-traumatic osteoarthritis is a notorious clinic problem. Its pathomechanism involves in immunologic, genetic and mechanical factors. Up to date, these factors, however, have only been limited as a generic disorder guidance and cannot be used for explanation of why only some of trauma patients develop the osteoarthritis. This uncertainty casts a shadow on the prevention and treatment of potential onset of cartilage degeneration. Based on previous work, we propose a novel mechanism of chondrocyte phenotypes and subsequent degeneration regulated by micro-stress environment. This application will provide further systematic validation of this finding by the use of theoretical analysis and experimental investigation to confirm the pivotal role of micro-stress in cartilage degeneration. Results will offer detailed mechanism of mechanical injury. More importantly, micro-stress environment will be considered as a new design parameter in regulation of chondrocyte phenotypes to improve the outcomes of prevention and treatment, to construct cartilage scaffold in tissue engineering, to optimize the strategy of genetic and molecular target interventions, and to accelerate the clinical applications of these emerging technologies.

创伤性骨关节炎的防治是临床上的一大难题，其发病机理涉及免疫因子、基因、机械损伤等多种因素。然而至今为止，相关机理研究大都停滞在对病因的描述和论证，并不能对软骨退变提供针对性的防治方案。课题组在前期工作中发现了一个尚未报道的发病机理：创伤可能是通过破坏软骨细胞所感应的正常微应力环境、产生局部微应力突变、诱发细胞表型转化、导致软骨结构功能的病理性退变。本项目将通过理论分析和试验检测系统性地完善这一发现，阐明损伤类型、微应力、软骨退变之间的相互关系，定义微应力突变在软骨退变中的特征。研究成果将不仅细化有关机械损伤的发病机理，更重要地是为下一步软骨退变防治提供了明确的思路。这包括：将微应力对细胞表型调控作为一个新的设计参数，用于改进临床现有的预防方法，设计满足微应力环境以促进软骨细胞和干细胞生长修复的组织工程支架，通过微应力环境优化基因和药物靶向治疗，加速这类新技术方法的临床应用。

创伤性骨关节炎的防治是临床上的一大难题。其发病机理涉及免疫因子、基因、机械损伤等多种因素。课题组在前期工作中发现创伤可能是通过破坏软骨细胞所感应的正常微应力环境、产生局部微应力突变、诱发细胞表型转化、导致软骨结构功能的病理性退变。本项目通过理论分析、动物试验和细胞试验系统性地完善这一发现，阐明损伤类型、微应力、软骨退变之间的相互关系，以及力学刺激对软骨细胞发生生物学作用的可能的分子机制。本研究结果将不仅细化有关机械损伤的发病机理，更重要地是为下一步软骨退变防治提供了新的思路。