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通过HCAR1/PI3K通路进行乳酸上调的NADPH依赖NOX4表达,有助于ROS诱导的骨关节炎冠状细胞损伤

Yi-Fan Huang¹, Guan Wang², Lu Ding³

¹Department of Orthopedics, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China; Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, Liaoning, China; Department of Orthopedics, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, China.

|September 9, 2023

概括

骨关节炎 (OA) 患者的乳酸盐水平升高会通过增加氧化应激和炎症而损害软骨. 针对乳酸盐的目标

科学领域:

生物化学生物化学
细胞生物学细胞生物学
病理学病理学病理学

背景情况:

代谢因素越来越多地与骨关节炎 (OA) 的发病有关.
乳酸的作用,一个关键的代谢物,在OA的发展及其潜在的机制需要澄清.
了解乳酸对状细胞功能的影响对于开发新型OA疗法至关重要.

研究的目的:

为了调查乳酸在骨关节炎的发病过程中的作用.
阐明乳酸酸通过哪些机制影响状细胞的功能,并有助于OA.
探索潜在的治疗策略,针对OA中的乳酸介导途径.

主要方法:

对OA患者和健康对照者的血清和突液乳酸水平的分析.
在体外研究中,使用用乳酸治疗的人类淋巴细胞来评估细胞反应.
在体内实验中,在OA的老鼠模型中进行了关节内乳酸注射的实验.
评估基因和蛋白质表达,活性氧物种 (ROS) 生成和软骨完整性.

主要成果:

在OA患者中,血清和突液中的乳酸水平升高,与代谢参数相关.
乳酸上调乳酸受体 (HCAR1) 和冠状细胞中的载体,通过NOX4激活增加ROS.
乳酸盐促进了冠状细胞损伤,代谢酶表达和炎症,同时降低了原蛋白合成;这些效应通过NOX4抑制或ROS清理而逆转.
牛乳酸在体内给药在OA大鼠模型中加剧了软骨损伤,这种效果通过NOX4抑制来减轻.

结论:

乳酸酸在骨关节炎的发病过程中发挥着重要作用,通过代谢和信号通路损害胆细胞的功能.
乳酸诱导的氧化应激和炎症有助于OA中的软骨降解.
针对乳酸介导通路,特别是NOX4,为骨关节炎提供了潜在的治疗途径.

关键词:

冠状细胞 (chondrocytes) 是一种细胞.乳酸盐是一种乳酸盐.在NADPH氧化酶4中.骨关节炎是一种骨关节炎.

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