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Epigenetics of osteoarticular diseases: recent developments

  • Review Article - Review on Pathogenesis
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Abstract

A variety of osteoarticular conditions possess an underlying genetic aetiology. Large-scale genome-wide association studies have identified several genetic loci associated with osteoarticular conditions, but were unable to fully account for their estimated heritability. Epigenetic modifications including DNA methylation, histone modification, nucleosome positioning, and microRNA expression may help account for this incomplete heritability. This articles reviews insights from epigenetic studies in osteoarticular diseases, focusing on osteoarthritis, but also examines recent advances in rheumatoid arthritis, osteoporosis, systemic lupus erythematosus (SLE), ankylosing spondylitis, and sarcoma. Genome-wide methylation studies are permitting identification of novel candidate genes and molecular pathways, and the pathogenic mechanisms with altered methylation status are beginning to be elucidated. These findings are gradually translating into improved understanding of disease pathogenesis and clinical applications. Functional studies in osteoarthritis, rheumatoid arthritis, and SLE are now identifying downstream molecular alterations that may confer disease susceptibility. Epigenetic markers are being validated as prognostic and therapeutic disease biomarkers in sarcoma, and clinical trials of hypomethylating agents as treatments for sarcoma are being conducted. In concert with advances in throughput and cost-efficiency of available technologies, future epigenetic research will enable greater characterisation and treatment for both common and rare osteoarticular diseases.

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Acknowledgments

The authors are grateful for the insight, suggestions, and constructive criticisms provided by Prof S.H. Ralston. Thank you.

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Bone Research Group, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK

    S. B. Roberts, L. De Ferrari, O. M. Albagha & D. M. Salter

  2. College of Medicine and Veterinary Medicine, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK

    E. Wootton

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  1. S. B. Roberts
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  2. E. Wootton
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  3. L. De Ferrari
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  4. O. M. Albagha
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  5. D. M. Salter
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Correspondence to S. B. Roberts.

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Roberts, S.B., Wootton, E., De Ferrari, L. et al. Epigenetics of osteoarticular diseases: recent developments. Rheumatol Int 35, 1293–1305 (2015). https://doi.org/10.1007/s00296-015-3260-y

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  • DOI: https://doi.org/10.1007/s00296-015-3260-y

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