Epigenetics in osteoarthritis and its implication for future therapeutics.

INTRODUCTION: Changes occurring in the chondrocyte gene that control articular cartilage are important for the onset and progression of osteoarthritis (OA). However, actual development of the disease may be also controlled by changes in epigenome. AREAS COVERED: Topics include the association of the three components of epigenetic modification, i.e., DNA methylation, histone modification, and microRNA expression, with the pathogenesis and progression of OA. The cross talk between genetics and epigenetics as well as the implication of epigenetics as a therapeutic measure for OA is also introduced. EXPERT OPINION: Epigenetic markers that detect various chondrocyte phenotypes, including those involving chondrogenic differentiation, articular cartilage homeostasis, and progression of OA, may provide a novel means to detect early OA. Recent report of dietary supplement such as glucosamine that prevents demethylation of promoters of inflammatory cytokine is encouraging. Although already available, the toxicity and off-target side effects of histone deacetylase inhibitors are concerns for benign nonlethal disease like OA. miRNA-based treatment may present another therapeutic modality without potentially detrimental off-target side effects. Future studies are needed to search for additional miRNA that can modulate the course of OA and to identify key targets of currently known miRNA that impact OA pathogenesis and disease progression.