Jumonji domain containing-3 (JMJD3) inhibition attenuates IL-1β-induced chondrocytes damage in vitro and protects osteoarthritis cartilage in vivo

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

“…Strikingly, KDM6B but not KDM6A expression was found to be increased in damaged cartilage compared to undamaged cartilage derived from the same knees of osteoarthritis patients undergoing knee replacement surgery [ 63 , 66 ], implicating KDM6B in articular cartilage damage and loss in osteoarthritis and contradicting the decreased KDM6B expression reported by Dai et al (2017) [ 64 ]. Factors thought to drive KDM6B upregulation in damaged cartilage in osteoarthritis include IL-1β and TGF-β, both of which were shown to induce KDM6B expression in cultured human articular chondrocytes (HACs) [ 66 ]. Accordingly, GSK-J4 inhibited TGFβ-responsive genes, including PAI1, and diminished the IL-1β-induced expression of the pro-inflammatory cytokines IL-6 and TNFα in HACs [ 64 , 66 ].…”

The JMJD3 histone demethylase inhibitor GSK-J1 ameliorates lipopolysaccharide-induced inflammation in a mastitis model

“…Another study suggests that the upregulation of JMJD3 enhances the proinflammatory response and immunopathology during respiratory syncytial virus infection ( 17 ). Moreover, the inhibition of JMJD3 attenuates interleukin (Il)-1β-induced chondrocytes damage and protects osteoarthritis cartilage ( 18 ). Here, we use the JMJD3-selective pharmacological inhibitor, GSK-J1, to clarify the role of JMJD3 in response to LPS-induced inflammation, exploring its molecular mechanisms of regulating inflammatory gene expression.…”

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs

“…Consistently, the expression of H3K27 demethylase KDM6B was reduced in human patients with OA, and KDM6B knockout in mice accelerated OA progression [ 138 ]. The KDM6B (JMJD3) inhibitor, GSK-J4, prevented ex vivo cartilage destruction in humans and suppressed disease development in a DMM-induced OA mouse model [ 140 , 144 ].…”