Etomidate ameliorated advanced glycation end-products (AGEs)-induced reduction of extracellular matrix genes expression in chondrocytes.

Osteoarthritis (OA) is a rheumatic disease common in the elderly. AGEs are the end products of glycation reactions and play an important role in the development of OA. Etomidate is a general anesthesia-inducing agent recently reported to exert significant anti-inflammatory effects. The present study aims to explore the protective effect of Etomidate against advanced glycation end-products (AGEs)-induced reduction of extracellular matrix gene expression in chondrocytes. In the present study, we found that AGEs significantly reduced the expression of Collagen II (COL2A1) and Aggrecan (ACAN) at the gene level. Furthermore, AGEs inhibited the expression of SRY-related high mobility group-box gene 9 (SOX-9), promoting the expression of COL2A1 and ACAN. COL2A1, ACAN, and SOX-9 in chondrocytes were significantly elevated by treatment with Etomidate alone. Consistently, Etomidate ameliorated AGEs-induced downregulation of COL2A1, ACAN, and SOX-9 in a dose-dependent manner. Importantly, we found that knockdown of SOX-9 eliminated the beneficial effects of Etomidate against AGEs-induced decrease in COL2A1 and ACAN genes. Based on these findings, we demonstrated that Etomidate could ameliorate AGEs-induced reduction of extracellular matrix gene expression in chondrocytes by upregulating SOX-9.