cGAS-STING aggravates cartilage degradation by promoting glycolysis in temporomandibular joint osteoarthritis.

This article investigates the role of the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway in the progression of temporomandibular joint osteoarthritis (TMJOA). The study demonstrates that abnormal mechanical stress on condylar chondrocytes induces mitochondrial DNA leakage into the cytoplasm, activating the cGAS-STING pathway, which in turn promotes glycolysis and exacerbates cartilage degradation by disrupting extracellular matrix (ECM) homeostasis. Pharmacological inhibition or genetic silencing of STING alleviated cartilage damage and subchondral bone erosion in experimental TMJOA models, while overexpression of the glycolytic enzyme hexokinase 2 (HK2) reversed these protective effects, highlighting glycolysis as a key mediator of STING-driven pathology. These findings establish a mechanistic link between mechanical stress, innate immune signaling, and metabolic reprogramming in TMJOA, suggesting that targeting the cGAS-STING pathway or glycolysis may offer therapeutic potential for this condition.