HMGB2在颞下颌关节髁突软骨“封闭”中的作用及调控机制

The superfacial zone (SZ) of articular cartilage can form an effective protective layer as a "seal" to prevent fluid loss and deep cartilage damage induced by mechanical stress. The high-mobility group box 2 (HMGB2), which specially expressed in SZ, has a similar distribulation compared with proteoglycan-4 (PRG4) can regulate cell survival of SZ. The reduction or absence of HMGB2 contributed to degeneration of articular cartilage or the development of OA , which suggesting HMGB2 play an important role in the maintenance of seal function of SZ. At present, the HMGB2 in the temporomandibular joint (TMJ) has not been reported In our preliminary experiments, we found that HMGB2 also specially expressed in cells of the superfacial zones in TMJ condylar cartilage. However, the role of HMGB2 in the condylar cartilage alterations after disc displacement is unclear. In this study, the expression of HMGB2, positioning and molecular mechanisms will be observed, the role of HMGB2 in adaptive alteration of the condylar cartilage after ADD and the regulation mechanism of HMGB2 in the progression and prognosis of ADD will be explored by animal model and in vitro methods. The study will be expected to give us some help to investigate the pathogenesis of temporomandibular joint disorder (TMD) and find new therapeutic targets.

受到应力时，关节软骨表层(SZ)能形成一个有效的封闭和保护层，阻止软骨深层液体的流失和损伤。HMGB2在SZ的表达具有特异性，且能调控SZ细胞的生存，与PRG4的表达有明显相关性。其表达的减少或缺失与关节软骨的退行性变及骨关节病发生密切相关，提示HMGB2对维持SZ的"封闭"作用有重要意义。目前，有关HMGB2在颞下颌关节（TMJ）中的研究还未见报导，预实验发现在TMJ髁突软骨的表面几层细胞中，HMGB2也特异性表达，但HMGB2在关节盘前移位(ADD)髁突软骨改建中是否也发挥着"封闭"作用尚不清楚。本课题拟通过建立ADD动物模型及体外细胞培养等方法来对HMGB2的表达、定位及调控机制进行研究，探索HMGB2在ADD后髁突软骨改建中的作用及其对ADD病程发展和转归的调控机制，以期对我们认识颞下颌关节紊乱病(TMD)的发病机制，寻找TMD新的治疗靶点及方案提供理据。

受到应力时，关节软骨表层(SZ)能形成一个有效的封闭和保护层，阻止软骨深层液体的流失和损伤。HMGB2在SZ的表达具有特异性，且能调控SZ细胞的生存，与PRG4的表达有明显相关性。其表达的减少或缺失与关节软骨的退行性变及骨关节病发生密切相关，提示HMGB2对维持SZ的“封闭”作用有重要意义。目前，有关HMGB2在颞下颌关节（TMJ）中的研究还未见报导。本通过建立ADD动物模型及体外细胞培养等方法来对HMGB2的表达、定位及调控机制进行研究，探索HMGB2在ADD后髁突软骨改建中的作用及其对ADD病程发展和转归的调控机制，HMGB2能使骨髓间充质干细胞维持在未分化（不成熟）状态，并且能阻止软骨细胞成熟、衰老向肥大软骨细胞分化。研究表明，关节盘移位或髁突软骨受到持续静压力后，HMGB2的表达受到抑制，软骨细胞可能加速分化，成熟，衰老，并向肥大软骨细胞分化。Wnt/β-catenin路径可能参与HMGB2对软骨细胞代谢及生物学行为的调控。该研究成果对我们认识颞下颌关节紊乱病(TMD)的发病机制，寻找TMD新的治疗靶点及方案有一定的意义。