咬合异常致颞下颌关节软骨退变的Wnt5a机制研究

Temporomandibular joint disorder (TMD) is a common disease in oral department. Osteoarthrosis (OA) is the most serious type of TMD. The dedifferentiation of chondrocytes in OA articular cartilage contributes significantly to the loss of articular cartilage matrix and the degeneration of articular cartilage. Wnt5a plays an important role in physiological chondrocytes differentiation, especially in chondrocytes hypertrophy. In our previous study, we found that unilateral anterior crossbite (UAC) led to OA-like changes in TMJ condylar process and dedifferentiation of chondrocytes, with down-regulation of Wnt5a expression level. This study aims to elucidate the mechanisms that the abnormal biologic loading UAC may promote the dedifferentiation of articular chondrocytes by down-regulating Wnt5a signaling in the cartilage of TMJ condyle, leading to the degradation of TMJ articluar cartilage. On the basis of preliminary studies, using rat model of UAC and primary chondrocytes as the object, we performed histomorphological and molecular-biological technologies to investigate the the contribution of Wnt5a reduction in pathological chondrocytes dedifferentiation, especially in the cartilage degradation of TMJOA from tissue/cell level to molecular level. Furthermore, we attempt to ameliorate cartilage degeneration by up-regulating Wnt5a in articular cartilage through intraarticular injection. This study may provide new ideas for TMJOA treatment.

颞下颌关节紊乱病（TMD）是口腔科常见疾病，骨关节病（OA）是TMD中最严重的类型。OA关节软骨细胞去分化是关节软骨基质丢失和关节软骨退变的重要原因。Wnt5a在生理性软骨细胞分化特别是肥大化过程中发挥着重要作用。前期研究中我们发现，前牙单侧反牙合（UAC）可导致TMJ髁突发生OA样改变，软骨出现去分化，伴Wnt5a表达降低。为了明确异常生物力UAC是否通过下调TMJ髁突软骨中的Wnt5a信号促进关节软骨细胞去分化，导致关节软骨的退变，本课题拟在前期研究基础上，以UAC大鼠模型和原代软骨细胞模型为研究对象，应用组织形态学和分子生物学等方法，从组织、细胞到分子水平探讨Wnt5a的下调在病理性软骨细胞去分化，特别是TMJOA软骨退变中的作用。进而通过关节腔内注射的方法增强关节软骨中的Wnt5a信号，改善异常生物力引起的软骨退变，以期为TMJOA的治疗提供新的思路。