title: Epigenetic mechanisms underlying the aberrant catabolic and anabolic activities of osteoarthritic chondrocytes.
abstract: The development of disease-modifying pharmacologic therapy for osteoarthritis currently faces major obstacles largely because the pathogenetic mechanisms for the development of osteoarthritis remain unclear. Previous studies suggest that the alterations in expression of catabolic and anabolic genes in articular chondrocytes may be involved in the pathogenesis of osteoarthritis. However, the regulatory mechanisms for gene expression in osteoarthritic chondrocytes are largely unknown. The objective of this review is to highlight the recent studies on epigenetic regulation of gene expression in the development of osteoarthritis. The review will begin with current understanding of epigenetic mechanisms, especially the newly emerging areas including the regulatory role of non-coding RNAs in gene expression and crosstalk among the epigenetic mechanisms. The main content of this review focuses on the significance of epigenetic regulation of the expression of catabolic and anabolic genes in osteoarthritic chondrocytes, including the regulatory roles of various epigenetic mechanisms in the expression of genes for specific matrix-degrading proteinases, cytokines, and extracellular matrix proteins. Recent novel findings on the epigenetic regulation of specific transcription factor genes are particularly important for the understanding of osteoarthritis pathogenesis, as these transcription factors may act as upstream regulators of multiple catabolic and anabolic genes. In conclusion, these recent advances in epigenetic studies have shed light on the importance of epigenetic regulation of gene expression in the development of osteoarthritis, leading to a better understanding of the epigenetic mechanisms underlying the pathogenesis of osteoarthritis. This may promote the development of new epigenetics-based strategies for the treatment of osteoarthritis. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.
authors.affiliation: Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, Kansas City, Kansas, USA.
authors.forename: Mingcai
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, Kansas City, Kansas, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Egan
authors.affiliation: Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, Kansas City, Kansas, USA; Department of Biochemistry & Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA. Electronic address: jwang@kumc.edu.
authors.forename: Jinxi
authors.initials: J
authors.lastname: Wang
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000276:immunology; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000276:immunology; D017364:Collagenases / Q000235:genetics / Q000276:immunology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D019175:DNA Methylation; D010450:Endopeptidases / Q000235:genetics / Q000276:immunology; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics* / Q000276:immunology; D006801:Humans; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology; D010003:Osteoarthritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D022661:RNA, Untranslated / Q000235:genetics / Q000276:immunology; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000276:immunology
chemical_list: D053674:Aggrecans; D050659:Core Binding Factor Alpha 1 Subunit; D016207:Cytokines; D006657:Histones; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D022661:RNA, Untranslated; C493709:RUNX2 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D003094:Collagen; D010450:Endopeptidases; D017364:Collagenases; C083641:aggrecanase
keywords: Cytokine; Epigenetics; Gene expression; Osteoarthritis; Proteinase; Transcription factor