Epigenetics in rheumatoid arthritis: a primer for rheumatologists.
Epigenetic anomalies are emerging as key pathogenic features of rheumatoid arthritis (RA). The effect of epigenetics in RA ranges from contributing to complex disease mechanisms to identifying biomarkers for early diagnosis and response to therapy. This review focuses on three key epigenetic areas in RA, namely DNA methylation, histone modification, and expression and/or function of microRNAs. Epigenomics studies of DNA methylation have identified alterations of genome-wide DNA methylation in cells from patients with rheumatoid arthritis. Histone modification studies have focused on histone acetylation, which tends to be increased in RA. Preclinical studies show that inhibitors of histone deacetylases are effective in cellular and animal models of RA. Genome-wide and candidate microRNA surveys identified increased or reduced expression of selected microRNAs in rheumatoid arthritis. These microRNA are either pro or anti-inflammatory in multiple cell types or affect osteoclast physiology and the pathogenesis of bone erosion. Defining epigenetic contributions to the pathogenesis of RA, especially in combination with understanding genetic associations, could lead to novel therapy and a clearer understanding of disease risk.
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA, nunzio@liai.org.
Nunzio
N
Bottini
Gary S
GS
Firestein
D000107:Acetylation; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism
D018501:Antirheumatic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D035683:MicroRNAs