The Epigenomic Landscape in Osteoarthritis

Abstract

Purpose of Review 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. Recent Findings 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. Summary 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.

Prioritization of PLEC and GRINA as Osteoarthritis Risk Genes Through the Identification and Characterization of Novel Methylation Quantitative Trait Loci

“…DNA methylation at CpG dinucleotides is an epigenetic process used by the cell to regulate gene expression, and it can amplify or attenuate the impact of an expression quantitative trait locus (QTL) (7)(8)(9). Our group has previously shown this in the context of GDF5, rs143383, and CpG sites located close to the SNP (10).…”

Increased susceptibility to develop spontaneous and post-traumatic osteoarthritis in Dot1l-deficient mice

“…Epigenetic processes maintain the specific cellular phenotype essential for the articular chondrocytes to ensure joint homeostasis, maintain tissue integrity and cope with challenges such as tissue injury or ageing 2e4 . Losing epigenetic control in the joint increases the susceptibility to develop osteoarthritis (OA) 1,5,6 .…”

Future Aspects of Clinical Osteoarthritis Therapies in the Continuum of Translational Research

“…Aus diesen Erkenntnissen ergeben sich potenziell neue therapeutische Therapieansätze, wie die Histon-Deacetylase-Inhibitoren, die in derartige epigenetische Pathomechanismen eingreifen könnten [10]. Nicht codierende Ribonukleinsäuren modifizieren nachweislich katabole Stoffwechselprozesse in Chondrozyten und stellen auf zellulärer Ebene einen sowohl pathophysiologischen als auch therapeutisch relevanten Akteur dar [19]. Die Autophagozytose von Chondrozyten ist eine weitere Stoffwechselauffälligkeit, die mit vermehrtem Zelluntergang und Knorpeldegeneration verbunden ist [20].…”