Abstract
An increasing number of studies show that besides the inherited genetic architecture (that is, genomic DNA), various environmental factors significantly contribute to the etiology of rheumatoid arthritis. Epigenetic factors react to external stimuli and form bridges between the environment and the genetic information-harboring DNA. Epigenetic mechanisms are implicated in the final interpretation of the encoded genetic information by regulating gene expression, and alterations in their profile influence the activity of the immune system. Overall, epigenetic mechanisms further increase the well-known complexity of rheumatoid arthritis by providing additional subtle contributions to rheumatoid arthritis susceptibility. Although there are controversies regarding the involvement of epigenetic and genetic factors in rheumatoid arthritis etiology, it is becoming obvious that the two systems (genetic and epigenetic) interact with each other and are ultimately responsible for rheumatoid arthritis development. Here, epigenetic factors and mechanisms involved in rheumatoid arthritis are reviewed and new, potential therapeutic targets are discussed.
Highlights
More than 10 years after the completion of the human genome sequencing project [1] and numerous genomewide association studies (GWAS) [2], we still do not fully understand the genetic basis of rheumatoid arthritis (RA)
We found that VX-680, an Aurora kinase-specific inhibitor, significantly reduced the severity of arthritis and promoted B cell apoptosis in the proteoglycan-induced arthritis (PGIA) model of RA
We have demonstrated the beneficial effect of specific Aurora kinase and histone acetyltranferases (HATs) inhibitors [20], and histone deacetylases (HDACs) inhibitors have been tested by other groups [30] in preclinical studies, unlike in the cancer field, there is still no epigenetics-based drug on the market of RA therapeutics
Summary
More than 10 years after the completion of the human genome sequencing project [1] and numerous genomewide association studies (GWAS) [2], we still do not fully understand the genetic basis of rheumatoid arthritis (RA). Histone acetylation and methylation exert their effects on gene expression by regulating the accessibility of DNA for transcription factors. Epigenetic alteration in rheumatoid arthritis synovial cells Early studies found widespread DNA hypomethylation in RA synovial fibroblasts, including hypomethylation of the promoter of the CXCL12 gene [15] and the LINE1 retrotransposons [16] that are repetitive elements normally repressed by DNA methylation.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
