Cgas-Sting Aggravates Cartilage Degradation By Promoting Glycolysis In Tmjoa

To investigate the role of cGAS-STING pathway induced by the abnormal mechanical stress in the degeneration of condylar cartilage during temporomandibular joint osteoarthritis (TMJOA). The expression pattern of cGAS-STING was examined in condyle cartilage from unilateral anterior crossbite (UAC) mice to uncover its potential role in TMJOA. The H-151 injected TMJOA mice and PBS-treated controls were used to clarify the effect of cGAS-STING on cartilage degradation. Primary condylar chondrocytes were exposed to mechanical loading and transfected with short hairpin RNA against Sting to explore the mechanisms of cGAS-STING on the energy metabolism and extracellular matrix (ECM) degradation in chondrocytes. The Hk2-overexpressing lentivirus was applied to determine the effect of cGAS-STING-promoted glycolysis both in vivo and in vitro. Mechanical stress exerted on condyle chondrocytes induced dsDNA leakage from mitochondria to cytoplasm to activate STING. Upon activation, STING exacerbated cartilage degradation by suppressing the anabolism of cartilage ECM and accelerating the catabolic activity. Furthermore, the promoted glycolysis in chondrocytes was identified as a central mechanism in the onset of TMJOA, with critical rate-limiting enzymes downstream of STING. Our study identified the crucial role of cGAS-STING-promoted glycolysis in condylar cartilage degradation and the therapeutic significance of STING-targeted therapy in TMJOA.