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Fig. 5 | Clinical Epigenetics

Fig. 5

From: Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature

Fig. 5

KDM6B inhibition in rheumatoid arthritis. Rheumatoid arthritis is a chronic inflammatory disease of the joints characterised by synovial hyperplasia, inflammation and bone erosion. KDM6B is implicated in platelet-derived growth factor BB (PDGFBB)-induced proliferation and migration of fibroblast-like synoviocytes, a process that underlies hyperplasia of the synovial membrane. Through inhibition of KDM6B, GSK-J4 inhibits the expansion and migratory capacity of fibroblast-like synoviocytes to attenuate synovial hyperplasia. Synovial inflammation in rheumatoid arthritis is driven by the release of pro-inflammatory cytokines, including tumour necrosis factor α (TNFα) and interferon γ (IFNγ), from macrophages and natural killer (NK) cells. GSK-J4 inhibits the production of these cytokines to dampen the inflammatory response in rheumatoid arthritis. Bone erosion in rheumatoid arthritis is mediated by bone-resorbing osteoclasts, the differentiation of which is supported by NK cells. By inhibiting KDM6B in NK cells, GSK-J4 impairs the ability of NK cells to promote the differentiation of monocytes to osteoclasts, protecting arthritic joints from bone erosion. This figure was created in BioRender.com

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