CoREST基因在骨关节炎软骨组织中的表达、分布和意义

Differential expression and distribution of CoREST in osteoarthritic cartilage

目的:观察RE-1元件辅助沉默因子(CoREST)基因在正常和骨关节炎(OA)膝关节软骨组织中的表达和分布,分析CoREST基因表达下调对OA的病理意义。方法:取材膝关节正常(n=10)和OA(n=12)软骨组织,提取软骨细胞并包埋制备切片,应用real-time PCR技术对比CoREST基因在正常和OA软骨细胞中表达水平的总体差异,应用原位杂交技术观察CoREST基因在正常/OA软骨表、中、深各层组织中的表达和分布的特点。结果:CoREST基因在OA软骨细胞中的表达水平显著降低64.6%(P<0.01)。CoREST基因广泛表达于正常软骨组织的表层、中层和深层,以中层表达最为显著,其次为深层和表层。在OA软骨组织中,CoREST基因在浅层细胞簇部分细胞中表达水平升高,在深层潮线状细胞柱中表达水平普遍降低。结论:CoREST基因在正常和OA软骨组织细胞中的差异表达和分布与文献报道的X型胶原基因的组织学表达一致。结合前期研究成果,我们认为CoR-EST的生物功能可能与OA软骨细胞的终末分化相关。

AIM： To analyze the role of RE-1 silencing transcription factor corepressor（CoREST） in the pathogenesis of osteoarthritis（OA） by observing the differential expression and distribution of CoREST gene in the normal and osteoarthritic knee cartilages. METHODS： The samples of knee cartilage were obtained from the normal donors（n=10） and the patients undergoing total knee arthroplasty with the diagnosis of OA（n=12）.The chondrocytes were isolated and paraffin sections were prepared.The expression levels of CoREST gene were determined in the normal and osteoarthritic chondrocytes by real-time PCR.The mRNA expression and distribution of CoREST in the individual layers,including the superficial,middle and deep layer of the normal and OA cartilage,were observed by the method of in situ hybridization. RESULTS： Compared with normal chondrocytes,CoREST gene expression was down-regulated by 64.6%（P0.01） in OA chondrocytes.CoREST mRNA was generally expressed in all the superficial,middle and deep layers of the normal cartilage,in which the highest was in the middle layer and then in the deep and superficial layers.In OA cartilage,CoREST mRNA expression was up-regulated dominantly in the cell clusters of the superficial layer,whereas down-regulated in the cell columns of the deep layer. CONCLUSION： The expression and distribution of CoREST gene between normal and OA chondrocytes are similar to those of the reported type X collagen.Based on the achievements of our previous study,we consider that the biological function of CoREST is correlated with the terminal differentiation of OA chondrocytes.