【摘要】 目的 研究骨关节炎患者关节软骨中DNA甲基化的特征，分析甲基化基因的表达在骨关节炎发生发展中的作用。方法 收集2018年3月—2019年1月在新疆医科大学附属第一医院关节中心3例接受全膝人工关节置换术的骨关节炎(Osteoarthritis, OA)患者(OA组),3例膝关节软骨正常截肢患者(对照组)软骨组织标本。采用Illumina Infinium Methylation EPIC Bead Chip(850K芯片)对软骨进行甲基化分析。应用InCroMAP软件进行关节软骨中全基因组DNA甲基化及mRNA表达扩增谱的整合途径富集分析。基于DAVID数据库进行基因本体论(Gene ontology, GO)分析和京都基因及基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)分析。结果 单基因分析结果显示，本研究共获得1 299个差异甲基化基因；整合DNA甲基化的mRNA表达谱发现，64个基因显著改变，包括远中缺失同源盒基因5(DLX5)、同源异型盒基因5(HOXA5)、软骨酸性蛋白1(CRTAC1)和可溶性富含半胱氨酸结构域的清道夫受体蛋白(SSC5D);GO分析发现，上述基因功能与免疫应答、炎症反应、细胞增殖等有关；KEGG分析发现，上述基因介导与OA发病密切相的丝裂原活化蛋白激酶(MAKP)信号通路和Hippo信号通路。结论 OA生物信息学分析发现可能的异常甲基化差异表达基因和信号通路，这可能会对OA发生和发展过程中的表观遗传学机制的阐明提供新的思路。更多还原

【Abstract】 Objective To investigate the characteristics of DNA methylation in articular cartilage in patients with osteoarthritis and toanalyze the role of methylation gene expression in occurrence and progression of osteoarthritis. Methods 3 patients with osteoarthritis(OA) who underwent total knee arthroplasty in the orthopaedic centerof the hospital from March 2018 to January 2019 were selected as OA group, and 3 patients with amputation(normal knee cartilage) were selected as control group. The genome-wide methylation profiles were determined byIllumina Infinium MethylationEPIC BeadChip,measuring the methylation state of over 850K CpG sites. Integrative pathway enrichment analysis ofgenome-wide DNA methylation and mRNA expression profiles conducted in articular cartilage was performed by InCroMAP software. Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were performed based on DAVID database. Results Single gene analysis showed that 1 299 differentially methylated genes were obtained in the study; The mRNA expression profile of integrated DNA methylation found that 64 genes were significantly altered,including Dlx5,HOXA5,CRTAC1and SSC5D; Go analysis showed that the functions of thegenes were related to immune response,inflammatory reaction and cell proliferation; KEGG analysis found that the above genes mediate mitogen activated protein kinase(MAKP) signaling pathway and Hippo signaling pathway closely related to pathogenesis of osteoarthritis. Conclusion OA bioinformatics analysis revealed possible aberrant methylation of differentially expressed genes and signaling pathways,which may shed new light on epigenetic mechanisms withinvolving OA initiation and development.更多还原