Cyanidin-3-O-glucoside chloride inhibits cartilage degeneration and inflammation in TMJOA via YAP/NF-κB signaling pathway.

This study investigated the therapeutic potential and underlying mechanisms of cyanidin-3-O-glucoside chloride (C3G) in regulating cartilage matrix metabolism and inflammation in temporomandibular joint osteoarthritis (TMJOA) induced by compressive force overload. A bilateral crossbite (BAC) mouse model of TMJOA was established and treated with intra-articular C3G administration, and structural as well as pathological alterations were assessed using micro-computed tomography (micro-CT) and immunohistochemistry (IHC). In vitro, ATDC5 cells were subjected to compressive force (3 g cm-2 for 24 h). Western blot and qRT-PCR were performed to evaluate the expression of cartilage matrix-associated proteins, YAP/NF-κB signaling molecules, and the pro-inflammatory cytokine IL-1β, while protein colocalization was examined by dual immunofluorescence staining. Pharmacological inhibitors of YAP (verteporfin) and NF-κB (BAY 11-7082) were applied to confirm pathway involvement. The results demonstrated that C3G markedly attenuated cartilage destruction and inflammation in TMJOA mice. In ATDC5 cells, compressive force activated YAP/NF-κB signaling, suppressed COL2A1 and SOX9, and upregulated MMP13 and IL-1β expression, whereas these deleterious effects were reversed by verteporfin and BAY 11-7082. Moreover, intra-articular administration of C3G significantly downregulated MMP13 and IL-1β expression, enhanced COL2A1 expression, and increased cartilage thickness in vivo. Collectively, these findings indicate that C3G confers protection against TMJOA by inhibiting cartilage matrix degradation, promoting extracellular matrix deposition, and suppressing inflammation through blockade of the YAP/NF-κB signaling axis, thereby highlighting C3G as a promising therapeutic candidate for the management of TMJOA.