机械负荷和超度是骨昼夜时钟每日重新设置的提示
Michal Dudek1,2,3, Dharshika R J Pathiranage1,2,3, Beatriz Bano-Otalora2
1Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.
Nature communications
|November 14, 2023
概括
每天的机械负荷和透变化作为局部线索,在骨组织中重置昼夜节律. 这一发现揭示了一种新的机制,用于维持软骨和椎间盘中身体的内部时钟.
科学领域:
- 时间生物学 时间生物学
- 骨生物学 骨生物学
- 机械生物学 机械生物学
背景情况:
- 哺乳动物的昼夜节律是由一个多振荡器系统调节的,该系统由光线和食等环境线索同步.
- 对于昼夜阶段调整的组织特异生理线索已被假设但未被确定.
- 局部机械和透信号在调节组织水平昼夜节律中的作用仍然在很大程度上未被探索.
研究的目的:
- 调查机械负荷和透挑战是否可以作为骨组织中昼夜钟的局部时间线索.
- 阐明这些生理刺激所导致的昼夜节律重置的分子机制.
- 为了确定这些线索在年轻和老化的骨组织中是否有效.
主要方法:
- 对软骨和椎间盘组织的体内和体外研究.
- 应用机械负荷和高透/低透条件的生理范围.
- RNA测序 (RNAseq) 和生物化学分析以确定涉及的分子途径.
主要成果:
- 每天的机械负荷和相关的超度会在骨组织中重置昼夜时钟阶段和振幅.
- 超度,但不是低度,在年轻和老化的骨组织中重置昼夜钟.
- 这些刺激诱导全基因组表达节律基因,并涉及PLD2-mTORC2-AKT-GSK3β信号轴.
结论:
- 每天的机械负荷和由此产生的透振荡是骨昼夜节律的真实组织特定时间线索.
- 这发现了一种用于同步局部组织时钟与全身昼夜调节的新机制.
- 了解这些线索对于保持骨健康和潜在地治疗与年龄有关的骨疾病至关重要.
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