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TLR4通过增强NLRP3-MAVS表达和相互作用来调解骨质细胞中葡萄糖脂毒性诱导的线粒体功能障碍

Ximei Shen¹, Xiaoyuan Chen², Shuai Zhong²

¹Deprtment of Endocrinology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Department of Endocrinology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Clinical Research Center for Metabolic Diseases of Fujian Province, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Fujian Key Laboratory of Glycolipid and Bone Mineral Metabolism, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Diabetes Research Institute of Fujian Province, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China; Metabolic Diseases Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.

International immunopharmacology

|March 18, 2025

概括

糖尿病性骨损失涉及线粒体功能障碍. 高葡萄糖和脂质激活托尔类受体4 (TLR4),导致骨质母细胞功能受损和糖尿病的骨质损失.

科学领域:

生物化学生化学
细胞生物学细胞生物学
内分泌学在内分泌学.

背景情况:

糖尿病性骨损失与由抑制骨质细胞分化的葡萄糖脂毒性引起的线粒体功能障碍有关.
连接葡萄糖脂毒性与线粒体损伤的精确分子途径尚未完全理解.

研究的目的:

研究托尔类受体4 (TLR4) 在葡萄糖脂毒性诱导的线粒体功能障碍和骨质细胞分化中的作用.
阐明TLR4在糖尿病骨损失中调解这些效应的分子机制.

主要方法:

在葡萄糖脂质毒性条件下对骨质母细胞的蛋白质组分析.
在体外实验涉及TLR4敲击和骨质母细胞过度表达的实验.
在体内研究使用TLR4淘汰赛糖尿病大鼠模型.
评估线粒体功能,细胞亡和骨质母细胞分化标志物.

主要成果:

葡萄糖脂毒性高调节骨质细胞中的TLR4表达,与线粒体功能障碍相关.
TLR4的激活导致NLRP3和MAVS的表达和相互作用增加,促进ROS的产生,ATP合成受损和亡.
降低TLR4可改善葡萄糖脂毒性诱导的线粒体功能障碍和骨质细胞亡.
在糖尿病大鼠中,TLR4淘汰会显著减轻骨质损失,改善线粒体和骨质蛋白质的表达.

结论:

葡萄糖脂毒性激活TLR4,启动一个涉及NLRP3-MAVS相互作用的级联,导致线粒体功能障碍和抑制骨质细胞分化.
这种TLR4介导的途径是糖尿病患者骨质减少的关键因素.
准TLR4可能为糖尿病骨质疏松症提供治疗策略.

关键词:

葡萄糖脂质毒性葡萄糖脂质毒性马夫斯 (MAVS) 是一种动物.线粒体功能线粒体功能在NLRP3中,NLRP3是NLRP3中的一个.在TLR4中,

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