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

本研究发现了几种与类风湿关节炎（RA）发病机制相关的新表观遗传学改变。本研究中使用的是从关节置换治疗患者的滑膜组织中获得的滑膜成纤维细胞。转录组分析显示RA滑膜成纤维细胞中一些重要分子的mRNA显著升高，例如MMPs、IL-6和IL-8。染色质免疫沉淀分析显示，这些分子在滑膜成纤维细胞RA与对照组相比，骨关节炎（OA）的异常组蛋白修饰。令人感兴趣的是，向这些细胞中加入炎性细胞因子会诱导这些基因的转录显著增加。这些数据表明，组蛋白修饰可能有助于在RA中观察到的关节炎的发病机制。

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.