线粒体反应性氧物种在骨中介质细胞中的作用机制
Md Mohsin Ali1, Intawat Nookaew2,3, Ana Resende-Coelho1
1Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
bioRxiv : the preprint server for biology
|April 8, 2025
概括
线粒体ROS通过破坏骨形成,导致骨质疏松症. 准线粒体ROS,衰老细胞和NAD+可能会对与年龄相关的骨质损失产生联合益处.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 老年学是一门学科.
背景情况:
- 与衰老相关的骨损失与线粒体的活性氧物种 (ROS),降低的NAD+和细胞衰老有关.
- 对于ROS导致骨质损失的精确体内机制仍然不完全理解.
研究的目的:
- 研究线粒体ROS在骨老化中的作用,通过在骨质细胞系细胞中遗传删除线粒体抗氧化酶Sod2.
- 阐明ROS对细胞衰老,NAD+水平和骨代谢的影响.
主要方法:
- 在骨质细胞系细胞中生成Sod2条件淘汰赛小鼠 (Sod2ΔOsx1).
- 评估骨质量,线粒体功能,NAD+水平和细胞衰老标志物.
- 对骨介质细胞的单细胞RNA测序分析,以确定受影响的信号通路.
主要成果:
- Sod2ΔOsx1小鼠的骨质较低,线粒体呼吸功能受损,NAD+水平降低.
- 服用NAD+前体改善了线粒体功能in vitro,但没有拯救骨质in vivo.
- ROS没有显著影响衰老标志物,但破坏了副甲状腺激素信号传递,铁代谢和骨介质细胞中的蛋白质稳定.
结论:
- 线粒体ROS通过超出细胞衰老的机制,包括关键代谢和信号通路的破坏,促进与年龄相关的骨质损失.
- 针对线粒体ROS,衰老细胞和NAD+水平的联合治疗策略可能有效地对抗骨质疏松症.
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