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依托咪酯改善糖基化终产物(AGEs)诱导的软骨细胞细胞外基质基因表达减少。

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

机构信息

Department of Anesthesiology, Outpatient and Emergency, Tianjin Hospital, Tianjin, China.

Department of Anus& Intestine Surgery, Tianjin Hospital, Tianjin, China.

出版信息

Bioengineered. 2021 Dec;12(1):4191-4200. doi: 10.1080/21655979.2021.1951926.

Abstract

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 () and Aggrecan () 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. , and in chondrocytes were significantly elevated by treatment with Etomidate alone. Consistently, Etomidate ameliorated AGEs-induced downregulation of , 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 . Based on these findings, we demonstrated that Etomidate could ameliorate AGEs-induced reduction of extracellular matrix gene expression in chondrocytes by upregulating SOX-9.

摘要

骨关节炎(OA)是一种常见于老年人的风湿性疾病。AGEs 是糖基化反应的终产物,在 OA 的发展中起重要作用。依托咪酯是一种最近报道具有显著抗炎作用的全身麻醉诱导剂。本研究旨在探讨依托咪酯对软骨细胞中晚期糖基化终产物(AGEs)诱导的细胞外基质基因表达减少的保护作用。在本研究中,我们发现 AGEs 显著降低了基因水平上的 Collagen II ( ) 和 Aggrecan () 的表达。此外,AGEs 抑制了 SOX-9 基因的表达,促进了 COL2A1 和 ACAN 的表达。单独用依托咪酯处理可显著上调软骨细胞中的 、 和 。同样,依托咪酯以剂量依赖性方式改善了 AGEs 诱导的 、 和 SOX-9 下调。重要的是,我们发现敲低 SOX-9 消除了依托咪酯对 AGEs 诱导的细胞外基质基因表达减少的有益作用。基于这些发现,我们证明依托咪酯可以通过上调 SOX-9 来改善 AGEs 诱导的软骨细胞细胞外基质基因表达减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4635/8806553/cdb524b0a6ff/KBIE_A_1951926_UF0001_OC.jpg

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