从多尺度组织力学角度探究骨性关节炎发病机理

Osteoarthritis (OA) is a prevalent joint disorder in the elderly and the leading cause of physical disability, which seriously affects public health. The origin and related pathology of OA is still under debate, and there is no reliable technique for its early diagnosis. It was reported that the mechanical properties of the various joint tissues are sensitive to OA’s pathological change, suggested that the tissue mechanics is suitable for tissue lesion detecting. In our previous studies, we developed the rate jump method that can effectively eliminate the viscoelastic effects during mechanical testing and the individual trabecula segmentation (ITS, developed by Prof, ED Guo, one of Co-I) that can precisely measure the structural parameters of trabecular bone. In this study, we will employ the two techniques to synchronously and quantitively monitor the multiscale mechanical and structural changes of various joint tissues during the initiation and progression of OA, with the purpose to figure out the exact tissue that OA initial from and the sequence of various tissue lesions. The related biochemical factors will also be monitored during OA. Combining the mechanical, structural and biochemical information, we will further investigate the causal relationship and corresponding mechanism among the various tissue lesions in OA. In addition, the collected mechanical and structural results of cancellous bone will be used for exploring the possible OA early diagnosis technique. The mechanical change that is more sensitive for tissue lesions will be used to determine the structural diagnostic thresholds of OA. It is believed that the present study will lead to further understanding of OA’s pathology and help the development of its early diagnosis technique.

骨性关节炎（osteoarthritis，OA）是一种高致残老年退行性骨科疾病，严重影响公众健康。目前，对OA病源及病理仍存在较大争议，并缺乏早期诊断手段。OA中关节各组织力学均存在明显变化，可用以检测病变发生。本项目拟基于成熟的骨性关节炎动物模型，利用团队研发的可消除力学测量过程中粘弹性效应的率跳跃方法（rate-jump method）及项目主要参与人郭向东教授独有的松质骨细微结构定量分析技术-单骨小梁分割技术（individual trabecula segmentation，ITS），同步监测各组织在OA病程中的多尺度力学及结构，以不同层面的力学特性改变时序确定病源组织及组织间的发病次序；结合生化因子监测，探索组织病变间相互作用机制。此外，将结合松质骨力学及结构学数据，以力学突变确定结构学诊断阈值，探索OA早期诊断技术。本研究将加深对OA病理认识，促进早期诊断技术的发展。

骨性关节炎是极为常见的慢性骨科疾病，严重影响患者的生活质量并有极高的致残率，其发病率随年龄增加。随着我国老龄化程度增加，骨性关节炎将严重影响我国的公众健康。研究对骨性关节炎发病过程的软骨多尺度力学行为进行研究，并对其相应病理进行了探索。通过项目的研究，我们基本确定在引入骨性关节炎第二日即开始出现的软骨细胞力学变化为最早的骨性关节炎发病标志，而软骨组织微观力学在病程中的拐点可能是骨性关节炎不可逆发展的起点。依据项目发现，我们开发了系列生物活性物质及生物材料应对骨性关节炎，均取得良好效果。