关节软骨稳态的破坏与OA的发生关系密切，但其具体机制尚未阐明。本课题组前期研究发现，成骨细胞转录因子Osterix在下颌髁突软骨中被敲除后，髁突软骨层增厚，软骨基质大量堆积，提示Osterix的缺失使得髁突软骨稳态偏向软骨基质的合成代谢，因而将Osterix敲除可能会修复颞下颌关节骨关节炎（TMJOA）进展过程中导致的软骨基质丧失从而使疾病过程得以逆转。本项目拟在前期研究基础上，通过将条件性基因敲除动物模型与TMJOA手术模型结合，在体内模拟Osterix缺失条件下关节炎的进展过程，利用Micro-CT、SEM和免疫组化等手段分析其在TMJOA进展过程中的作用，体外通过原代提取髁突软骨细胞并利用IL-1β诱导模拟OA环境，利用Western blot、Microarray和染色质免疫共沉淀等技术进一步明确Osterix对下颌髁突软骨稳态调控的分子机制，为今后TMJOA的基因治疗提供新思路。

The disruption of cartilage homeostasis is closely related to osteoarthritis (OA), while the mechanism behind this remains unclear. Our previous study revealed that condylar cartilage became thickened and cartilage matrix was highly accumulated after the deletion of Osterix in mandibular condylar cartilage. Thus, the condylar cartilage homeostasis turns to anabolic activities resulted from the deficiency of Osterix. This indicates that the deletion of Osterix in mandibular condylar cartilage could restore the cartilage matrix loss during the development of temporomandibular joint osteoarthritis (TMJOA) so that the disease could be rescued. This project is based on our previous study and we combine the conditional gene knockout animal model with the TMJOA surgery model to investigate the role of Osterix in the development of TMJOA. We take advantage of Micro-CT and SEM as well as IHC to analyze the phenotype. On the other hand, primary mandibular condylar chondrocyte will be isolated and in vitro OA will be simulated by IL-1β induction. Combined approaches including Western blot, Microarray and CHIP are used to clarify the molecular mechanism how Osterix regulate the homeostasis of mandibular condylar cartilage. This work is trying to provide some new clues for the TMJOA gene therapy in the future.