Epigenetics in the pathogenesis of RA.
Epigenetic modifications can stably alter gene expression and have been shown to be important in the maintenance of cell type-specific functions as well as in cell differentiation, e.g., in T and B cell maturation. In RA, alterations in DNA methylation, histone modifications, and microRNA expression have been found in immune as well as in stromal cells. These changes in the epigenome in RA patients influence key inflammatory and matrix-degrading pathways and are suspected to play a major role in the pathogenesis of RA. In this manuscript, we explain the basic mechanisms of epigenetics, review studies that analyzed epigenetic changes in RA, and assess their potential as therapeutic targets.
Center of Experimental Rheumatology, University Hospital of Zurich, Wagistrasse 14, 8952, Schlieren, Switzerland. caroline.ospelt@usz.ch.
Caroline
0000-0002-9151-4650
C
Ospelt
Center of Experimental Rheumatology, University Hospital of Zurich, Wagistrasse 14, 8952, Schlieren, Switzerland.
Steffen
S
Gay
Center of Experimental Rheumatology, University Hospital of Zurich, Wagistrasse 14, 8952, Schlieren, Switzerland.
Kerstin
K
Klein
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D006657:Histones; D035683:MicroRNAs
DNA methylation; Histone modifications; MicroRNA; Rheumatoid arthritis; Synovial fibroblasts