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Emerging epigenetic targets in rheumatoid arthritis

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Abstract

Rheumatoid arthritis is a complex disorder that is characterized by irreversible and progressive destructions of joints, but its exact etiology remains mainly unknown. The occurrence and the progression of the disease entirely depend on environmental and genetic factors. In recent years, various epigenetic changes involving DNA methylation, histone modification, miRNA, X-chromosome inactivation, bromodomain, sirtuin, and many others were identified that were found to be linked to the activation and the aggressive phenotype in rheumatoid arthritis. Epigenetics is found to be one of the root causes, which brings changes in the heritable phenotype and is not determined by changes in the DNA sequences and understanding these epigenetic mechanisms and the pathogenesis of the disease can help in understanding the disease and various other possible ways for its control and/or prevention. The various epigenetic modification occurring are reversible and can be modulated by drugs, diet, and environmental factors. This article focuses on various epigenetic factors involved in the pathogenesis of rheumatoid arthritis. Further, various epigenetic therapies that might be successful in inhibiting these epigenetic modifications are summarized. Several therapeutic agents alter the epigenetic modifications occurring in various diseases and many of the epigenetic therapies are under pre-clinical and clinical trial. However, exploring these epigenetic prognostic biomarkers would give a broader perspective and provide more ideas and knowledge regarding the process and pathways through which the diseases occur, and also combining various therapeutic agents would show more beneficial and synergistic effects.

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Abbreviations

AICDA:

Activation-induced cytidine deaminase

BETi:

Bromodomain and extra-terminal

CXCL12:

CXC motif chemokine ligand 12

DNMT:

DNA methyltransferase

FLS:

Fibroblast-like synoviocytes

Foxp3:

Forkhead box p3

HDAC:

Histone deacetylase

IFNg:

Interferon gamma

IL:

Interleukin

IRAK1:

Interleukin q receptor-associated kinase 1

IκBs:

Inhibitors of kappa B

KDM6B:

Lysine (K)-specific demethylase 6B

miR:

Mirco RNA

NFκB:

Nuclear factor-kappa B

OASF:

Osteoarthritis synovial fibroblast

PBMC:

Peripheral blood mononuclear cells

PI3K:

Phosphoinositide 3-kinase pathway

RA:

Rheumatoid arthritis

RASF:

Rheumatoid arthritis synovial fibroblast

SF:

Synovial fibroblast

SF:

Synovial fibroblast

TF:

Transcription factors

TGFb:

Transforming growth factor beta

TLR2:

Toll like receptor 2

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  1. Department of Pharmacology, SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (West), Mumbai, 400056, India

    Reema R. Barik & Lokesh Kumar Bhatt

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  1. Reema R. Barik
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  2. Lokesh Kumar Bhatt
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Conceptualization: [LKB]; Writing—original draft preparation: [RRB]; Writing—review and editing: [LKB].

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Correspondence to Lokesh Kumar Bhatt.

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Barik, R.R., Bhatt, L.K. Emerging epigenetic targets in rheumatoid arthritis. Rheumatol Int 41, 2047–2067 (2021). https://doi.org/10.1007/s00296-021-04951-y

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