The Epigenomic Landscape in Osteoarthritis

Tommie C. Simon, Matlock A. Jeffries

Epigenomics has emerged as a key player in our rapidly evolving understanding of osteoarthritis. Historical studies implicated epigenetic alterations, particularly DNA methylation, in OA pathogenesis; however, recent technological advances have resulted in numerous epigenome-wide studies examining in detail epigenetic modifications in OA. The purpose of this article is to introduce basic concepts in epigenetics and their recent applications to the study of osteoarthritis development and progression. Epigenetics describes three major phenomena: DNA modification via methylation, histone sidechain modifications, and short noncoding RNA sequences which work in concert to regulate gene transcription in a heritable fashion. Cartilage has been the most widely studied tissue in OA, and differential methylation of genes involved in inflammation, cell cycle, TGFβ, and HOX genes have been confirmed several times. Bone studies suggest similar findings, and the intriguing possibility of epigenetic changes in subchondral bone during many OA processes. Multiple studies have demonstrated the involvement of certain noncoding RNAs, particularly miR-140, in OA development via modulation of key catabolic factors. Although much work has been done, much is still unknown. Future epigenomic studies will no doubt continue to widen our understanding of extraarticular tissues and OA pathogenesis, and studies in animal models may offer glimpses into epigenome alterations in the earliest stages of OA.