Gene therapy for temporomandibular joint osteoarthritis

本研究旨在阐明关节软骨退化的机制，探讨结缔组织生长因子(CTGF)用于关节软骨修复的可能性。首先，我们建立了真正的机械应力诱导的兔TMJ关节软骨退化模型。实验兔采用重复强迫张口(RFJO)，每天3小时，连续5天。关节组织学观察，术后7d关节软骨部分脱落，关节软骨细胞反应性边缘增生，软骨下骨区软骨细胞嵌套性增殖。这些结果表明，RFJO方案在不需要任何手术干预的情况下，可以在兔TMJ诱导出明显的OA样病变，该模型可能有助于阐明TMJOA软骨降解的机制。其次，我们研究了重组腺病毒转导的CTGF/HCS24对体外培养的兔关节软骨细胞的影响。当携带CTGF/Hcs24基因的腺病毒感染RAC细胞时，RAC细胞表达CTGF/Hcs24基因，并产生CTGF/Hcs24蛋白。RAC细胞比对照细胞合成更多的蛋白多糖。

The purposes of this research are to clarify the mechanism of cartilage degradation in osteoarthritis (OA) and to investigate the possibility of gene therapy for articular cartlige restoration using connective tissue growth fector (CTGF).First, we establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive forced jaw opening (RFJO) 3 hours/day for 5 days was applied. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the RFJO period. These results suggest the RFJO protocol without any surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.Second, we investigated the effects of CTGF/Hcs24 transduced by recombinant adenoviruses on the rabbit articular cartilage (RAC) cells in vitro. When RAC cells were infected with adenoviruses caontaining the CTGF/Hcs24 gene, RAC cells expressed CTGF/Hcs24 mRNA and produced CTGF/Hcs24 protein. RAC cells synthesized more proteoglycan than the control cells.