Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage

Bone & Joint Research

article

A. He¹  Y. Ning¹  Y. Wen¹  Y. Cai²  K. Xu³  Y. Cai³  J. Han¹  L. Liu¹  Y. Du¹  X. Liang¹  P. Li¹  Q. Fan¹  J. Hao¹  X. Wang¹  X. Guo¹  T. Ma¹  F. Zhang¹ 

[1] 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;Department of Orthopaedics, The First Affiliated Hospital, Xi’an Jiaotong University Health Science Center;Department of Joint Surgery, Xi’an Hong-Hui Hospital, Xi’an Jiaotong University Health Science Center

关键词: Osteoarthritic cartilage;    DNA methylation profiles;    mRNA expression profiles;    Integrative analysis;   

DOI  :  10.1302/2046-3758.75.BJR-2017-0284.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimOsteoarthritis (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.Patients and MethodsGenome-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).ResultsWe 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).ConclusionWe 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.

【 授权许可】

CC BY-NC