Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The etiology of KBD remains unknown. In this study, we conducted an integrative analysis of genome-wide DNA methylation and mRNA expression profiles between KBD and normal controls to identify novel candidate genes and pathways for KBD. Articular cartilage samples from 17 grade III KBD patients and 17 healthy controls were used in this study. DNA methylation profiling of knee cartilage and mRNA expression profile data were obtained from our previous studies. InCroMAP was performed to integrative analysis of genome-wide DNA methylation profiles and mRNA expression profiles. Gene ontology (GO) enrichment analysis was conducted by online DAVID 6.7. The quantitative real-time polymerase chain reaction (qPCR), Western blot, immunohistochemistry (IHC), and lentiviral vector transfection were used to validate one of the identified pathways. We identified 298 common genes (such as COL4A1, HOXA13, TNFAIP6 and TGFBI), 36 GO terms (including collagen function, skeletal system development, growth factor), and 32 KEGG pathways associated with KBD (including Selenocompound metabolism pathway, PI3K-Akt signaling pathway, and TGF-beta signaling pathway). Our results suggest the dysfunction of many genes and pathways implicated in the pathogenesis of KBD, most importantly, both the integrative analysis and in vitro study in KBD cartilage highlighted the importance of selenocompound metabolism pathway in the pathogenesis of KBD for the first time.

大骨节病 (KBD) 是一种地方性慢性骨软骨病。KBD的病因尚不清楚。在这项研究中，我们对 KBD 和正常对照之间的全基因组 DNA 甲基化和 mRNA 表达谱进行了综合分析，以确定 KBD 的新候选基因和途径。本研究使用了来自 17 名 III 级 KBD 患者和 17 名健康对照的关节软骨样本。膝关节软骨的 DNA 甲基化分析和 mRNA 表达谱数据来自我们之前的研究。InCroMAP 用于对全基因组 DNA 甲基化谱和 mRNA 表达谱进行综合分析。基因本体（GO）富集分析由在线 DAVID 6.7 进行。定量实时聚合酶链反应 (qPCR)、蛋白质印迹、免疫组织化学 (IHC)、和慢病毒载体转染用于验证确定的途径之一。我们确定了 298 个常见基因（如 COL4A1、HOXA13、TNFAIP6 和 TGFBI），36 个 GO 术语（包括胶原蛋白功能、骨骼系统发育、生长因子）和 32 个与 KBD 相关的 KEGG 通路（包括硒化合物代谢通路、PI3K-Akt 信号通路）通路和 TGF-β 信号通路）。我们的结果表明与 KBD 发病机制有关的许多基因和通路功能障碍，最重要的是，综合分析和 PI3K-Akt 信号通路和 TGF-β 信号通路）。我们的结果表明与 KBD 发病机制有关的许多基因和通路功能障碍，最重要的是，综合分析和 PI3K-Akt 信号通路和 TGF-β 信号通路）。我们的结果表明与 KBD 发病机制有关的许多基因和通路功能障碍，最重要的是，综合分析和KBD 软骨的体外研究首次强调了硒化合物代谢途径在 KBD 发病机制中的重要性。