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Characterization of the cartilage DNA methylome in knee and hip osteoarthritis

Lookup NU author(s): Dr Michael Rushton, Dr Louise Reynard, Dr Matthew Barter, Ramsay Refaie, Kenneth Rankin, Professor David Young, Professor John Loughlin

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

Objective: The aim of this study was to characterise the genome-wide DNA methylation profile of osteoarthritis (OA) chondrocytes from both knee and hip cartilage, providing the first comparison of DNA methylation between OA and non-OA hip cartilage, and between OA hip and OA knee cartilage. Methods: The study was performed using the Illumina Infinium HumanMethylation450 BeadChip array, which allows the annotation of approximately 480,000 CpG sites. Genome-wide methylation was assessed in chondrocyte DNA extracted from 23 OA hip and 73 OA knee patients, and in 21 healthy hip controls. Results: Analysis revealed OA hip and hip controls have a unique methylation profile, with 5322 differentially methylated loci (DMLs) identified between the two groups. In addition, a comparison between OA hip and OA knee revealed 5547 DMLs between the two groups, including DMLs in several genes known to be involved in OA pathogenesis. We also show that OA hip samples cluster into two groups. In total 15239 DMLs were identified between the two clusters, with an enrichment of pathways involved in inflammation and immunity. Similarly, we confirm a previous report showing OA knee samples also cluster into two groups. Conclusion: We demonstrate that global DNA methylation using a high-density array can be a powerful tool in the characterisation of OA at the molecular level. Identification of pathways enriched in DMLs between OA-free and OA cartilage highlight potential etiological mechanisms that are involved in the initiation and/or progression of the disease and which could be therapeutically targeted.


Publication metadata

Author(s): Rushton MD, Reynard LN, Barter MJ, Refaie R, Rankin KS, Young DA, Loughlin J

Publication type: Article

Publication status: Published

Journal: Arthritis & Rheumatology

Year: 2014

Volume: 66

Issue: 9

Pages: 2450–2460

Print publication date: 01/09/2014

Online publication date: 26/08/2014

Acceptance date: 13/05/2014

Date deposited: 28/08/2014

ISSN (print): 2326-5191

ISSN (electronic): 2326-5205

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/art.38713

DOI: 10.1002/art.38713

PubMed id: 24838673


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