Disturbed Glycometabolism-Induced Chondrocyte Apoptosis Contributes to TMJOA.

OBJECTIVE

Elucidate the mechanism underlying chondrocyte apoptosis induced by abnormal glycometabolism in the early stages of temporomandibular joint osteoarthritis (TMJOA) and identify potential therapeutic targets.

DESIGN

Established TMJOA model by monosodium iodoacetate(MIA), a direct inhibitor of glyceraldehyde 3-phosphate dehydrogenase(GAPDH). Assessed the relationship between chondrocyte apoptosis and the levels of advanced glycation end products (AGEs) and their receptor (RAGE). Confirmed the apoptosis-inhibitory effect of AGEs by RAGE inhibitor FPS-ZM1. Verified the role of p38 in the up-regulation of cleaved caspase-3. Investigated the effect of glyceraldehyde 3-phosphate (G3P) in AGEs-RAGE pathway. verified the universality of the AGEs-RAGE pathway in occlusal interference-induced TMJOA.

RESULTS

In the early stages of TMJOA, chondrocyte apoptosis was associated with an upregulation of AGEs and RAGE. AGEs induced chondrocyte apoptosis by activating p38 through a RAGE-dependent pathway. Inhibition of GAPDH led to the accumulation of G3P, resulting in an upregulation of AGEs and RAGE. Inhibition of RAGE reversed chondrocyte apoptosis following GAPDH inhibition. Local joint injection of FPS-ZM1 alleviated TMJOA induced by both MIA and OI.

CONCLUSIONS

Altered glycometabolism can induce chondrocyte apoptosis through the AGEs-RAGE axis, suggesting that RAGE may serve as a therapeutic target for TMJOA.