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通过TREX1激活AP-1-依赖的c-Fos,驱动M2巨细胞两极分化,并减轻关节炎的进展

Shanbang Zhu¹, Xinzhe Feng², Jiabin Yuan³

¹Department of Orthopedics, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 305 Zhongshan East Road, Xuanwu District, Nanjing City, 210000, Jiangsu Province, China.

Cellular and molecular life sciences : CMLS

|June 24, 2025

概括

三个主要修复外核酶1 (TREX1) 缺乏症通过增加炎症和软骨损伤使骨关节炎恶化. TREX1调节巨细胞极化,为骨关节炎治疗提供了潜在的治疗点.

科学领域:

骨关节炎 (OA) 的发病因子
炎症和氧化应激作用的情况.
软骨的恒常性软骨的恒常性

背景情况:

炎症是骨关节炎的一个关键驱动因素.
TREX1在炎症反应和氧化应激中起着至关重要的作用.
重要的是研究TREX1在中间半月体 (DMM) 不稳定后的关节平衡中的功能.

研究的目的:

研究TREX1在维持关节平衡中的调节功能.
了解TREX1在DMM诱导的关节炎模型中的作用.
探索TREX1对巨细胞极化和状细胞功能的影响.

主要方法:

在DMM诱导的OA模型中使用了Trex1-Knockout (KO) 鼠标.
通过免疫光学和西欧涂抹来评估组织学和分子变化.
建立了巨细胞和红细胞的体外共同培养系统,以研究TREX1的调节机制.

主要成果:

TREX1缺乏症加剧了OA的进展,增加了氧化应激,炎症和软骨损伤.
在巨细胞中TREX1预处理减少了LPS诱导的慢性细胞亡和氧化应激.
在OA中,TREX1调节巨细胞极化,影响状细胞分化和矩阵稳态.

结论:

TREX1 影响巨细胞的两极分化,影响状细胞的功能和软骨的平衡.
TREX1成为骨关节炎治疗的潜在治疗标.
了解TREX1的作用对于开发新型OA疗法至关重要.

关键词:

AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 冠状腺细胞 (chondrocyte) 是一种细胞.巨细胞是一个巨细胞.骨关节炎是一种骨关节炎.在Trex1中,我们可以看到Trex1.

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