Nrf2通过ROS依赖机制缓解RANKL和M-CSF诱导的骨质细胞分化
Yang Yang1, Zhiyuan Liu2,3,4, Jinzhi Wu2,3,4
1Department of Rehabilitation, The First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang 110001, China.
Antioxidants (Basel, Switzerland)
|December 23, 2023
概括
核因子-红色素2相关因子2 (Nrf2) 缺乏通过增加活性氧物种 (ROS) 和c-FOS激活促进骨质细胞分化. 抗氧化剂抑制了这种效应,突出了Nrf2.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 核因子-红素2相关因子2 (Nrf2) 被认为是骨质细胞分化的负调节者.
- 在骨质细胞形成中Nrf2的作用背后的精确分子机制仍然不完全理解.
- 研究Nrf2,氧化应激和骨质细胞形成之间的相互作用对于理解骨代谢至关重要.
研究的目的:
- 阐明Nrf2在骨质细胞生成过程中调节抗氧化剂和活性氧物种 (ROS) 水平中的特定作用.
- 检查Nrf2缺乏对细胞质和线粒体ROS积累在分化骨质细胞中的影响.
- 确定下游信号通路,包括c-FOS激活,受Nrf2和ROS在骨质细胞分化中的影响.
主要方法:
- 使用骨髓衍生的巨细胞 (BMMs) 和RAW 264.7细胞用于体外骨质细胞分化模型.
- 在RANKL和M-CSF刺激下,在mRNA和蛋白质水平上评估Nrf2和抗氧化酶水平.
- 在野生类型和Nrf2缺乏细胞中测量了细胞质和线粒体ROS水平.
- 评估了外源抗氧化剂 (NAC,DPI,MitoQ) 和c-FOS抑制对骨质细胞分化的影响.
主要成果:
- 缺少Nrf2显著促进了BMM和RAW 264.7细胞中的骨质细胞分化.
- 在骨质细胞分化过程中,RANKL和M-CSF降低了Nrf2和下游抗氧化酶表达.
- 缺乏nrf2的细胞显示了细胞质和线粒体ROS积累的增加.
- 抗氧化剂和c-FOS抑制有效地抑制了因Nrf2缺乏症增加的骨质细胞分化.
- 升高的ROS促进了c-FOS酸化,推动了骨质细胞分化.
结论:
- Nrf2通过调节细胞内ROS水平,在抑制骨质细胞分化方面发挥着关键作用.
- Nrf2调节抗氧化酶,从而防止ROS积累和随后的c-FOS激活在骨质细胞形成过程中.
- 针对Nrf2-ROS-c-FOS轴提供了潜在的治疗策略,用于骨复苏性疾病.
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