Emerging epigenetic targets in rheumatoid arthritis.

Rheumatoid arthritis is a complex disorder that is characterized by irreversible and progressive destructions of joints, but its exact etiology remains mainly unknown. The occurrence and the progression of the disease entirely depend on environmental and genetic factors. In recent years, various epigenetic changes involving DNA methylation, histone modification, miRNA, X-chromosome inactivation, bromodomain, sirtuin, and many others were identified that were found to be linked to the activation and the aggressive phenotype in rheumatoid arthritis. Epigenetics is found to be one of the root causes, which brings changes in the heritable phenotype and is not determined by changes in the DNA sequences and understanding these epigenetic mechanisms and the pathogenesis of the disease can help in understanding the disease and various other possible ways for its control and/or prevention. The various epigenetic modification occurring are reversible and can be modulated by drugs, diet, and environmental factors. This article focuses on various epigenetic factors involved in the pathogenesis of rheumatoid arthritis. Further, various epigenetic therapies that might be successful in inhibiting these epigenetic modifications are summarized. Several therapeutic agents alter the epigenetic modifications occurring in various diseases and many of the epigenetic therapies are under pre-clinical and clinical trial. However, exploring these epigenetic prognostic biomarkers would give a broader perspective and provide more ideas and knowledge regarding the process and pathways through which the diseases occur, and also combining various therapeutic agents would show more beneficial and synergistic effects.