He A, Ning Y, Wen Y, Cai Y, Xu K, Cai Y, Han J, Liu L, Du Y, Liang X, Li P, Fan Q, Hao J, Wang X, Guo X, Ma T, Zhang F
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Department of Orthopaedics, The First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Bone Joint Res. 2018 Jun 5;7(5):343-350. doi: 10.1302/2046-3758.75.BJR-2017-0284.R1. eCollection 2018 May.
Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage.
Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID).
We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032).
We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA.: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. 2018;7:343-350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1.
骨关节炎（OA）由遗传和环境因素之间的复杂相互作用引起。表观遗传机制控制基因表达，并且可能调节OA转录组。我们进行了综合基因组分析，以确定骨关节炎软骨中的甲基化-基因表达关系。
使用Illumina Infinium HumanMethylation450 BeadChip（Illumina，加利福尼亚州圣地亚哥）对五名膝骨关节炎患者和五名健康对照者的关节软骨进行全基因组DNA甲基化分析。从基因表达综合数据库（GEO）获得另外三名骨关节炎患者和三名健康对照者关节软骨的其他独立全基因组mRNA表达谱。使用跨平台微阵列和通路软件的综合分析对DNA甲基化和mRNA表达谱进行综合通路富集分析。使用注释、可视化和综合发现数据库（DAVID）进行基因本体（GO）分析。
我们鉴定出1265个差异甲基化基因，其中145个与基因表达的显著变化相关，如DLX5、NCOR2和AXIN2（DNA甲基化和mRNA表达的所有p值均<0.05）。通路富集分析确定了26条与OA相关的通路，如丝裂原活化蛋白激酶（MAPK）信号通路（p = 6.25×10-4）、磷脂酰肌醇（PI）信号系统（p = 4.38×10-3）、缺氧诱导因子1（HIF-1）信号通路（p = 8.63×10-3）、泛酸和辅酶A（CoA）生物合成（p = 0.017）、表皮生长因子受体（ErbB）信号通路（p = 0.024）、肌醇磷酸（IP）代谢（p = 0.025）和钙信号通路（p = 0.032）。
我们鉴定出一组基因和生物学通路，其在OA患者和对照者之间的DNA甲基化和mRNA表达谱中均存在显著差异。这些结果可能为阐明OA发生发展机制提供新线索。作者：A. He、Y. Ning、Y. Wen、Y. Cai、K. Xu、Y. Cai、J. Han、L. Liu、Y. Du、X. Liang、P. Li、Q. Fan、J. Hao、X. Wang、X. Guo、T. Ma、F. Zhang。利用综合表观遗传和mRNA表达分析鉴定骨关节炎软骨中显著变化的基因和功能通路。2018；7：343 - 350。DOI：10.1302/2046 - 3758.75.BJR - 2017 - 0284.R1
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