The integrative analysis of DNA methylation and mRNA expression profiles confirmed the role of selenocompound metabolism pathway in Kashin-Beck disease
The integrative analysis of DNA methylation and mRNA expression profiles confirmed the role of selenocompound metabolism pathway in Kashin-Beck disease
复制标题
DNA甲基化和mRNA表达谱的综合分析证实了硒化合物代谢途径在大骨节病中的作用
DOI：
10.1080/15384101.2020.1807665
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发表时间：
2020-08-21
期刊：
影响因子：
4.3
通讯作者：
Xu, Peng
中科院分区：
文献类型：
--
作者：
Li, Ping;Ning, Yujie;Xu, Peng
大骨节病（KBD）是一种地方性慢性骨关节病。大骨节病的病因尚不清楚。在这项研究中，我们对大骨节病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，以确定新的候选基因和大骨节病的途径。本研究使用了17例III级KBD患者和17例健康对照者的关节软骨样本。膝关节软骨的DNA甲基化谱和mRNA表达谱数据来自我们之前的研究。使用InCroMAP对全基因组DNA甲基化谱和mRNA表达谱进行整合分析。基因本体（GO）富集分析采用在线DAVID 6.7软件。采用实时定量聚合酶链反应（qPCR）、Western blot、免疫组化（IHC）和慢病毒载体转染等方法验证其中一条途径。我们确定了298个与大骨病相关的常见基因（如COL4A1、HOXA13、TNFAIP6和TGFBI）， 36个氧化石墨烯术语（包括胶原功能、骨骼系统发育、生长因子）和32个与大骨病相关的KEGG通路（包括硒化合物代谢通路、PI3K-Akt信号通路和tgf - β信号通路）。我们的研究结果表明，大骨病的发病机制涉及许多基因和途径的功能障碍，最重要的是，无论是对大骨病软骨的综合分析还是体外研究，都首次强调了硒化合物代谢途径在大骨病发病机制中的重要性。
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 andin vitrostudy in KBD cartilage highlighted the importance of selenocompound metabolism pathway in the pathogenesis of KBD for the first time.