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Fig. 6 | Clinical Epigenetics

Fig. 6

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

Fig. 6

KDM6B inhibition in osteoarthritis. KDM6B is overexpressed in damaged cartilage in the knees of patients with osteoarthritis, a likely consequence of chondrocyte stimulation with IL-1β or TGFβ1. In osteoarthritis, chondrocytes upregulate the expression of the proteases MMP9, MMP13 and ADMATS5 in response to stimulation with IL-1β to promote cartilage damage and erosion. IL-1β also induces the expression of IL-6 and IL-8 in chondrocytes to create a pro-inflammatory milieu in osteoarthritis. Inhibition of KDM6B with GSK-J4 attenuates cartilage loss and inflammation in OA by suppressing these chondrocyte responses to IL-1β and TGFβ1. KDM6B also drives the expression of the cartilage components COL2A1 and aggrecan and the bone constituent COL10A1 during TGFβ3-mediated chondrogenic differentiation of mesenchymal stem cells, contributing to cartilage and bone synthesis, respectively. Inhibiting KDM6B would not promote the replacement of damaged cartilage and bone in osteoarthritis. This figure was created in BioRender.com

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