骨关节炎（OA）是重症颞下颌关节病患者的常见表现，其重要致病因素为软骨下骨吸收，但骨吸收机制不明。我们前期对颞下颌关节（TMJ）OA样变大鼠研究发现，髁突软骨下骨BMSC在TMJOA早期软骨下骨吸收中发挥重要促破骨效应。LncRNA-p21是我们筛选获得的在TMJOA髁突软骨下骨BMSC中显著下调的LncRNA，预实验显示：过表达LncRNA-p21可显著逆转TMJOA大鼠髁突软骨下骨BMSC的促破骨效应，这一逆转作用可被敲除β‑catenin阻断。提示LncRNA-p21通过β‑catenin在TMJOA软骨下骨丢失中发挥关键作用。本项目拟以TMJOA鼠及LncRNA-p21靶向调控鼠及其BMSC为模型，采用细胞共培养，基因敲除或过表达等技术系统研究LncRNAp21-βcatenin信号级联在TMJOA髁突软骨下骨病变中的作用机制，为临床治疗TMJOA提供新策略。

Osteoarthritis (OA) is the common manifestation of patients with severe temporomandibular disorders, and its important causative factor is subchondral bone resorption, but the mechanism of bone resorption is unknown. Our previous studies on the rat model of temporomandibular joint (TMJ) OA showed that the bone marrow mesenchymal stem cells (BMSC) from TMJ-OA condylar subchondral bone secreted high level of SDF-1 and RANKL, and could significantly promote the migration and activation of osteoclast precursor cells, indicating that BMSC plays an important role in promoting the subchondral bone resorption in TMJOA. Our microarray result showed that LncRNA-p21 was a significantly down-regulated LncRNA in the TMJOA condylar subchondral bone BMSCs comparing to the controls. In addition, overexpression of LncRNA-p21 significantly reversed the pro-osteoclastic effect of BMSC from the TMJOA condylar condyles, while this reversing effect could be blocked by the knockdown ofβ catenin. These results suggested that LncRNA-p21 plays a key role in the subchondral bone loss of TMJOA via β catenin. Using TMJOA mouse and LncRNA-p21 target regulatory mouse and their BMSC as the models, the present project will adopt the cell co-culture method, gene knockdown and overexpression method to study the pathomechanism of LncRNAp21-βcatenin signaling cascade in the development of the resorption of TMJOA condylar subchondral bone. This project will provide for new treatment strategies for TMJOA patients.