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循环节调节器PER1通过激活炎症基因来抑制骨质细胞生成
Nobuko Katoku-Kikyo1,2, Elizabeth K Vu1,3, Samuel Mitchell1,3
1Stem Cell Institute, University of Minnesota.
概括
昼夜调节器PER1通过控制炎症和骨质细胞形成来抑制骨损失. 准PER1可以治疗骨疾病,而不会破坏睡眠和清醒周期.
科学领域:
- 时间生物学 时间生物学
- 骨生物学 骨生物学 骨生物学
- 炎症 炎症是一种炎症.
背景情况:
- 扰乱昼夜节律与骨质疏松症等慢性疾病有关.
- 昼夜干扰对骨重塑的影响尚不清楚.
研究的目的:
- 研究核心昼夜调节器PER1在骨质细胞形成和骨质量调节中的作用.
- 阐明将昼夜节律扰乱与骨重塑联系起来的分子机制.
主要方法:
- 在小鼠骨干细胞和相关细胞中的Per1的有条件淘汰.
- 在实验室中研究了带有Per1枯竭的骨质细胞生成.
- 对基因表达的分析,包括炎症基因.
- 针对特定的炎症基因 (Nlrp3, Tlr8, Tlr9) 的 Knockdown 实验.
主要成果:
- 在骨质细胞中,Per1淘汰赛导致骨质量减少,骨质细胞增加,小鼠骨质细胞减少.
- 在实验室中,Per1的耗尽促进了骨质细胞形成,并降低了16个炎症基因的调节.
- 对Nlrp3,Tlr8或Tlr9的淘汰效应模仿了Per1的淘汰效应,这表明有机械联系.
- 佩尔2淘汰赛没有产生类似的结果,而佩尔1淘汰赛的小鼠保留了昼夜节律.
结论:
- PER1 作为骨质细胞形成的抑制剂,可能通过调节炎症基因.
- PER1是与昼夜干扰相关的骨疾病的潜在治疗标,例如骨质疏松症,类风湿性关节炎和骨关节炎.
- 研究结果显示,昼夜调节与炎症性骨疾病之间存在分子联系.
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