Alleviation of temporomandibular joint osteoarthritis by targeting RIPK1-mediated inflammatory signalling

Temporomandibular joint osteoarthritis (TMJOA), prevalent in adolescents and the elderly, has serious physical and psychological consequences. TMJOA is a degenerative disease of the cartilage and bone, mostly driven by inflammation, and synoviocytes are the first and most important inflammatory factor releasers. Receptor-interacting serine/threonine-protein kinase (RIPK1) promotes inflammatory response and cell death during an array of illnesses. This research aimed to explore the impacts of RIPK1 Inhibitor therapy in TMJOA and the mechanism of RIPK1 in inducing inflammation during TMJOA. Herein, inhibition of RIPK1 suppressed the elevated levels of inflammatory factors, nuclear factor kappa B (NF-κB), along with markers of Apoptosis and Necroptosis after tumour necrosis factor (TNF)-α/cycloheximide (CHX) treatment in synoviocytes. Moreover, inflammation models were constructed in vivo through complete Freund's adjuvant (CFA) induction and disc perforation, and the findings supported that RIPK1 inhibition protected TMJ articular cartilage against progressive degradation. RIPK1 regulates NF-κB activation via cellular inhibitor of Apoptosis proteins (cIAP), Apoptosis via Caspase-8, and Necroptosis via RIPK3/Mixed Lineage Kinase domain-like (MLKL) in synoviocytes, which in turn facilitates TMJOA inflammation progression.

Caspase-8; MLKL; RIPK1; RIPK3; TNF-α; cIAP.