pathogenic changes in histone modification and DNA methylation in synovial fibroblasts from RA joints

一些新的表观遗传学改变，与类风湿性关节炎(RA)的发病机制有关，在这个项目中被证明。本研究使用的滑膜成纤维细胞取自关节置换术患者的滑膜组织。转录组分析显示RA滑膜成纤维细胞中一些重要分子如MMPs、IL-6和IL-8的mRNAs水平显著升高。染色质免疫沉淀分析显示，与对照组相比，RA滑膜成纤维细胞中这些分子的组蛋白修饰异常。有趣的是，向这些细胞中加入炎性细胞因子可以显著增加这些基因的转录。这些数据表明，组蛋白修饰可能与类风湿关节炎的发病机制有关。

Several novel epigenetic changes, related to pathogenesis of rheumatoid arthritis (RA), have been demonstrated in this project. Used in this study weresynovial fibroblasts obtained from synovial tissues of patients under joint replacement therapy. Transcriptome analysis showed significant elevation of mRNAs of some of the important molecules, e.g.MMPs, IL-6 and IL-8, in RA synovial fibroblasts. Chromatin immunoprecipitation assays revealed abnormal histone modifications of these molecules in synovial fibroblasts from RA comparing with those from control, osteoarthritis (OA). Of interest was that addition of inflammatory cytokines to these cells induced dramatically increased transcription of these genes. These data suggest histone modifications may contribute to the pathogenesis of arthritis seen in RA.