Epigenetics in rheumatoid arthritis; fibroblast-like synoviocytes as an emerging paradigm in the pathogenesis of the disease.
Rheumatoid arthritis (RA) is characterized by immune dysfunctions and chronic inflammation that mainly affects diarthrodial joints. Genetics has long been surveyed in searching for the etiopathogenesis of the disease and partially clarified the conundrums within this context. Epigenetic alterations, such as DNA methylation, histone modifications, and noncoding RNAs, which have been considered to be involved in RA pathogenesis, likely explain the nongenetic risk factors. Epigenetic modifications may influence RA through fibroblast-like synoviocytes (FLSs). It has been shown that FLSs play an essential role in the onset and exacerbation of RA, and therefore, they may illustrate some aspects of RA pathogenesis. These cells exhibit a unique DNA methylation profile in the early stage of the disease that changes with disease progression. Histone acetylation profile in RA FLSs is disrupted through the imbalance of histone acetyltransferases and histone deacetylase activity. Furthermore, dysregulation of microRNAs (miRNAs) is immense. Most of these miRNAs have shown an aberrant expression in FLSs that are involved in proliferation and cytokine production. Besides, dysregulation of long noncoding RNAs in FLSs has been revealed and attributed to RA pathogenesis. Further investigations are needed to get a better view of epigenetic alterations and their interactions. We also discuss the role of these epigenetic alterations in RA pathogenesis and their therapeutic potential.
['Karami|Jafar|J|', 'Aslani|Saeed|S|', 'Tahmasebi|Mohammad Naghi|MN|', 'Mousavi|Mohammad Javad|MJ|', 'Sharafat Vaziri|Arash|A|', 'Jamshidi|Ahmadreza|A|', 'Farhadi|Elham|E|', 'Mahmoudi|Mahdi|M|0000-0002-8164-8831']
D000107:Acetylation D001172:Arthritis, Rheumatoid D019175:DNA Methylation D044127:Epigenesis, Genetic D005347:Fibroblasts D051548:Histone Acetyltransferases D006655:Histone Deacetylases D006657:Histones D006801:Humans D035683:MicroRNAs D062085:RNA, Long Noncoding D000070918:Synoviocytes
epigenetics rheumatoid arthritis fibroblast-like synoviocytes DNA methylation histone modifications noncoding RNA