通过HIF1α-PADI4途径激活骨髓ROS激活NETosis CD55+中间成熟中性粒细胞,以启动骨衰老
Yutong Guo1, Shengjie Cui2, Xi Wen1
1Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices& Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory For Dental Materials, Beijing, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|January 8, 2026
概括
骨髓中性质细胞结核病 (NETosis) 通过诱导骨髓 stromal 细胞的衰老来驱动骨衰老. 清除NETs (中性粒细胞外细胞陷) 缓解衰老,揭示了骨质疏松症治疗的目标.
科学领域:
- 免疫学 免疫学 免疫学
- 老年学是一门学科.
- 细胞生物学 细胞生物学
背景情况:
- 中性粒细胞结核病在衰老过程中失调.
- 骨髓NETosis在骨老化中的作用尚不清楚.
- 中性粒细胞异质性和骨髓炎症对NETosis的影响需要研究.
研究的目的:
- 调查老化骨髓中的NETosis.
- 确定NETosis和骨衰老之间的联系.
- 确定调节骨老化中NETosis的机制和细胞参与者.
主要方法:
- 使用了老化加速老鼠倾向6 (SAMP6) 模型.
- 在骨髓中性粒细胞中评估NETosis.
- 使用scRNA-seq来识别中性粒细胞子集.
- 进行细胞转移实验.
- 研究的分子通路 (ROS,HIF1α,PADI4).
主要成果:
- 在SAMP6骨髓中,NETosis高度激活.
- 释放的NETs诱导骨髓 stromal 细胞 (BMSC) 衰老,并损害骨质生成.
- 在SAMP6小鼠中,NET清除改善了骨老化.
- 一个CD55+中性粒细胞子集与上调的NETosis被确定并被证明可以诱导骨老化.
- 一个涉及ROS,CD55,HIF1α和PADI4的途径触发了NETosis.
结论:
- 在CD55+中性粒细胞中激活的NETosis启动了骨衰老.
- 在免疫失调和骨髓细胞衰老之间存在着炎症的恶性循环.
- 这项研究为骨质疏松症提供了潜在的治疗点.
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