Efficacy of HDAC inhibitors and epigenetic modulation in the amelioration of synovial inflammation, cellular invasion, and bone erosion in rheumatoid arthritis pathogenesis

Int Immunopharmacol. 2023 Sep:122:110644. doi: 10.1016/j.intimp.2023.110644. Epub 2023 Jul 14.


Rheumatoid arthritis (RA), an auto-immune disorder affected 1 % of the population around the globe. The pathophysiology of RA is highly concerted process including synovial hyperplasia, pannus formation, bone erosion, synovial cell infiltration in joints, and cartilage destruction. However, recent reports suggest that epigenetics play a pivotal role in the formation and organization of immune response in RA. Particularly, altered DNA methylation and impaired microRNA (miRNA) were detected in several immune cells of RA patients, such as T regulatory cells, fibroblast-like synoviocytes, and blood mononuclear cells. All these processes can be reversed by regulating the ubiquitous or tissue-based expression of histone deacetylases (HDACs) to counteract and terminate them. Hence, HDAC inhibitors (HDACi) could serve as highly potent anti-inflammatory regulators in the uniform amelioration of inflammation. Therefore, this review encompasses the information mainly focussing on the epigenetic modulation in RA pathogenesis and the efficacy of HDACi as an alternative therapeutic option for RA treatment. Overall, these studies have reported the targeting of HDAC1, 2 & 6 molecules would attenuate synoviocyte inflammation, cellular invasion, and bone erosion. Further, the inhibitors such as trichostatin A, suberoyl bis-hydroxamic acid, suberoyl anilide hydroxamic acid, and other compounds are found to attenuate synovial inflammatory immune response, clinical arthritis score, paw swelling, bone erosion, and cartilage destruction. Insight to view this, more clinical studies are required to determine the efficacy of HDACi in RA treatment and to unravel the underlying molecular mechanisms.

Keywords: Autoimmune disease; Histone deacetylase inhibitor; Joint inflammation; Rheumatoid arthritis; Synovial fibroblasts.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid*
  • Epigenesis, Genetic
  • Fibroblasts / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Inflammation / metabolism
  • Synovial Membrane / pathology
  • Synoviocytes* / metabolism


  • Histone Deacetylase Inhibitors