Therapeutic effect of Frzb on joint diseases

本研究旨在探讨Frzb对关节疾病的治疗作用及软骨细胞分化和凋亡在其发病机制中的作用。首先，为了阐明骨关节炎(OA)软骨细胞凋亡的机制，我们检测了热休克蛋白70(FISP70)的功能，该蛋白在骨关节炎的发病机制中起着关键作用。通过腺病毒载体将HSP70基因导入软骨细胞，可抑制NO或星形孢菌素诱导的软骨细胞凋亡。这些发现有助于阐明骨性关节炎的部分发病机制。其次，为了验证Frzb对关节疾病的治疗作用，我们研究了过表达Frzb对类风湿关节炎(RA)滑膜成纤维细胞和骨关节炎软骨下成骨细胞细胞因子表达的影响。用脂质体转染法将Frzb高表达到各原代细胞中。提取总β，用RT-PCR法检测IL-1、IL-6、IL-8和肿瘤坏死因子-α的表达。在骨性关节炎软骨下的成骨细胞中，可检测到内源性Frzb的表达，过度表达Frzb后，炎性细胞因子的表达减少。在RA的滑膜成纤维细胞中，细胞因子的表达没有明显变化。提示软骨下骨的异常分化可能参与了骨性关节炎的发病机制，Frzb基因可能是骨性关节炎的候选基因。从软骨细胞凋亡的角度探讨Frzb与HSP70的关系，阐明Frzb对实验性膝骨性关节炎的体内治疗作用，有待进一步研究。

The aim of this study is to investigate the therapeutic effect of Frzb on joint diseases and the mechanism of chondrocyte differentiation and apoptosis in their pathogenesis. Firstly, to elucidate the mechanism of chondrocyte apoptosis in osteoarthritis (OA), we examined the function of heat shock protein 70 (FISP 70), which was known to play a pivotal role in OA pathogenesis. HSP 70 was genetically transduced into chondrocytes by means of the adenovirus vector, and the treatment prohibited NO-or staurosporine-induced apoptosis. These findings help elucidate part of the pathogenesis of OA. Secondly, to demonstrate the therapeutic effect of Frzb on joint diseases, we investigate the influence of overexpressed Frzb on the cytokine expression by syonovial fibroblasts of rheumatoid arthritis (RA) and osteoblasts from subchondral bone of OA. Frzb was overexpressed into each primary cells by means of lipofection method. Total RNA was extracted and analyzed by RT-PCR method for IL-1β, IL-6,IL-8 and TNF-αmRNA expression. In osteoblasts from subchondral bone of OA, endogenous Frzb expression was detectable and the expression of inflammatory cytokines decreased after Frzb overexpression. In syonovial fibroblasts of RA, remarkable change of cytokine expression was not observed. These findings suggest that aberrant differentiation of subchondral bone can be involved in the pathogenesis of OA and Frzb can be therapeutic candidate gene of OA. Further research is necessary to find the relationship between Frzb and HSP 70 from the aspect of chondrocyte apoptosis and clarify in vivo therapeutic effect of Frzb on experimental OA in the rabbit knee.