Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Highly Accessed Review

Epigenetic contributions in the development of rheumatoid arthritis

Kerstin Klein*, Caroline Ospelt and Steffen Gay

Author affiliations

Center of Experimental Rheumatology, University Hospital Zurich and Zurich Center of Integrative Human Physiology, Gloriastrasse 23, CH-8091 Zurich, Switzerland

For all author emails, please log on.

Citation and License

Arthritis Research & Therapy 2012, 14:227  doi:10.1186/ar4074

Published: 9 November 2012

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic inflammation of the joints with severe pain and swelling, joint damage and disability, which leads to joint destruction and loss of function. Despite extensive research efforts, the underlying cause for RA is still unknown and current therapies are more or less effective in controlling symptoms but still fail to cure the disease. In recent years, epigenetic modifications were found to strongly contribute to the development of RA by affecting diverse aspects of the disease and modifying gene expression levels and behavior of several cell types, first and foremost joint resident synovial fibroblasts (SF). RASF are the most common cell type at the site of invasion. Owing to their aggressive, intrinsically activated phenotype, RASF are active contributors in joint damage. RASF are characterized by their ability to secrete cytokines, chemokines and joint-damaging enzymes. Furthermore, these cells are resistant to apoptosis, leading to hyperplasia of the synovium. In addition, RASF have invasive and migratory properties that could lead to spreading of the disease to unaffected joints. Epigenetic modifications, including DNA methylation and post-translational histone modifications, such as histone (de)acetylation, histone methylation and histone sumoylation were identified as regulatory mechanisms in controlling aggressive cell activation in vitro and in disease outcome in animal models in vivo. In the last 5 years, the field of epigenetics in RA has impressively increased. In this review we consider the role of diverse epigenetic modifications in the development of RA, with a special focus on epigenetic modifications in RASF.