近年人们逐渐关注软骨下骨在骨关节炎(OA)进程中的作用。大多数相关基础研究都是基于创伤性OA模型。本项目关注更高发病率的雌激素缺乏OA，其特殊性在于：OA初期软骨缺损缓慢，尚具有修复的可能；雌激素影响软骨下骨重建，软骨下骨可能发挥更重要作用。目前尚无系统研究软骨与软骨下骨在雌激素缺乏OA初期代谢变化特点及相互作用规律的报道。预实验结果提示，雌激素缺乏OA初期，软骨下骨的力学生物学特性改变在先，可能是造成软骨发生退变的重要诱发因素。本项目拟采用OVX-OA模型观察并定量分析软骨与软骨下骨变化规律。利用有限元模拟、力学实验、组织形态分析结果揭示软骨下骨改变与软骨退变的相关性，说明软骨下骨的重要作用。同时，采用OVX成骨细胞与正常软骨细胞共培养方法探明雌激素在其中影响及可能机制。本项目希望通过探索软骨下骨在OVX-OA初期的作用与机制，为雌激素缺乏OA的早预防与治疗提供思路与理论依据。

Nowadays, people realize that The subchondral bone plays significant biomechanical and biochemical roles in osteoarthritis (OA). However, most related studies were based on the post-trauma OA model. Estrogen deficiency induced OA attracts our interests due to its specialties: cartilage degeneration is slow; the degeneration might be recoverable; the subchondral bone is more important due to estrogen's effects on bone. There is yet no study at present which systematically investigates changes of cartilage and subchondral bone along time at the initial stage of estrogen deficiency induced OA. This project aims, using the OVX-OA rat model, to investigate the changes of morphology, mechanical properties, biochemical parameters for both cartilage and subchondral bone, quantify their relationship and explore the effects of subchondral bone under different levels of estrogen at the initial stage of OVX-OA. Finite element analysis will be applied to simulate the effects of subchondral bone change on healthy cartilage and study the mechanical mechanism in the crosstalk between cartilage and subchondral bone. Osteoblast-chondrocyte cocultural system will be used to investigate the possible biochemical mechanism about how estrogen treatment regulates interaction between OVX osteoblasts and normal chondrocytes. Through this project, we hope to clarify the role of subchondral bone in cartilage degeneration in estrogen deficiency induced OA, and provide evidences for subchondral bone as a treatment target at the initial stage of estrogen deficiency induced OA.