Epigenetic mechanisms underlying the aberrant catabolic and anabolic activities of osteoarthritic chondrocytes. (October 2015)

• Record Type: Journal Article
• Authors: Zhang, Mingcai; Egan, Brian; Wang, Jinxi
• Is Part Of: International journal of biochemistry & cell biology. Volume 67(2015:Oct.)
• Page Start: 101
• Page End: 109
• Publication Date: 2015-10
• Subjects: Epigenetics -- Osteoarthritis -- Gene expression -- Proteinase -- Transcription factor -- Cytokine; OA osteoarthritis -- ACs articular chondrocytes -- ncRNA non-coding RNAs -- DNMTs DNA methyltransferases -- TETs ten-eleven translocation proteins -- CGIs CpG islands -- HATs histone acetyltransferases -- HKMTs histone lysine methyltransferases -- LSD1 Lysine-specific demethylase 1 -- KDM4A while lysine-specific demethylase 4A -- mRNA messager RNA -- miRNAs microRNAs -- siRNAs short interfering RNAs -- piRNAs piwi-interacting RNAs -- IL-1β interlukin 1-β -- ECM extracellular matrix -- ADAMTS a disintegrin and metalloproteinase with thrombospondin motifs -- MMP13 matrix metalloproteinase 13 -- COL2A1 type II collagen -- COL9A1 type IX collagen -- RA rheumatoid arthritis -- TNF-α tumor necrosis factor-α -- Runx2 Runt-related transcription factor 2 -- Cbfa1 core-binding factor subunit alpha-1 -- SHH sonic hedgehog -- ACAN aggrecan -- NFAT Nuclear Factor of Activated T-cells -- Jhdm2a Jmjc-containing histone demethylase-2a; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.04.019
• Languages: English
• ISSNs: 1357-2725

Abstract

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.