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SP0018 DNA Methylation and Osteoarthritis
  1. L.N. Reynard
  1. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Abstract

One mechanism of epigenetic gene regulation is DNA methylation, which involves the addition of a methyl group to a cytosine base by DNA methyltransferase enzymes and occurs predominantly at CpG dinucleotides in mammalian cells. DNA methylation within the gene promoter regions is associated with gene repression through effects on transcription factor binding and recruitment of chromatin remodelling complexes. In contrast, gene body methylation positively correlates with gene expression and has been implicated in transcription from alternative promoters as well as alternative splicing.

DNA methylation changes occur during aging and in response to environmental factors including diet and smoking. Furthermore, aberrant DNA methylation patterns have been implicated in the aetiology of many common human disease including cancer, RA and SLE. Over the last 10 years, there has been increasing interest in the potential contribution of DNA methylation in the molecular mechanisms underlying OA pathogenesis, which will be the focus of this talk. I will begin by examining candidate gene studies that have focused on the relationship between cartilage promoter methylation, transcription factor binding and mRNA expression of genes implicated in OA, including the OA susceptibility gene GDF5, the chondrogenic transcription factor SOX9 and the matrix degrading enzyme MMP13. I will then review the key findings from genome-wide DNA methylation studies of osteoarthritic cartilage and bone. These DNA methylome studies have shown that hip and knee cartilage are epigenetically distinct, and have highlighted the potential importance of cartilage inflammation and TGFβ signalling in OA pathogenesis. I will finish by discussing areas for future DNA methylation studies in OA research and, given that OA is a disease of the whole joint, the potential to extend these analyses to other tissue compartments.

Disclosure of Interest None declared

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