香烟烟雾通过Nrf2/HERC2轴驱动的铁灭症破坏了骨质生成-基生成平衡
Wenjing Li1, Li Song1, Fanxuan Zhang1
1Tongde Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
Free radical biology & medicine
|September 12, 2025
概括
香烟烟雾破坏骨健康,导致铁失调和铁,损害骨的形成. 激活Nrf2通路为吸烟相关的骨质疏松症提供了潜在的治疗方法.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 骨生物学 骨生物学 骨生物学
背景情况:
- 暴露在香烟烟雾 (CS) 中会破坏铁的平衡,这是骨质疏松症的关键因素.
- 将CS暴露与骨损失联系在一起的确切机制在很大程度上是未知的.
研究的目的:
- 阐明CS暴露导致骨质损失的机制.
- 调查核因子E2相关因子2 (Nrf2) / HECT和含有E3无素蛋白联酶2 (HERC2) 途径的RLD域在CS诱导的骨损伤中的作用.
主要方法:
- 在体内研究中使用了暴露于CS提取物的野生类型和Nrf2敲击小鼠.
- 在体外研究中使用骨髓衍生中介细胞干细胞 (BMSCs),用CS治疗,有或没有Nrf2激动剂.
- 分析包括骨矿物质密度,组织形态测量,分子标记物和Nrf2/HERC2通路评估.
主要成果:
- 通过NCOA4介导的费里丁,CS暴露诱导了骨和BMSC中的铁亡,促进了脂肪生成和抑制了骨质生成.
- CS上调KEAP1,抑制Nrf2核转位,从而降低HERC2的表达,导致铁自.
- Nrf2或HERC2缺乏症加剧了CS诱导的骨损失和铁; Nrf2与bardoxolone的激活逆转了这些影响.
结论:
- 通过失调Nrf2/HERC2轴,CS诱导骨质损失,导致铁亡并损害骨质生成.
- 药物激活Nrf2为吸烟相关的骨质疏松症提供了一个新的治疗策略.
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