在周期性机械拉伸负荷下,YAP机械传导对中酶干细胞骨质生成的作用是由ROCK调节的
Eunju Kim1, Brandon D Riehl1, Tasneem Bouzid1
1Department of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, NE, United States.
Frontiers in bioengineering and biotechnology
|January 26, 2024
概括
动态机械拉伸激活介质干细胞 (MSC) 中的yes相关蛋白 (YAP),促进它们的骨质分化. 这个过程涉及ROCK-F-actin通路,对于骨组织工程至关重要.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 机械生物学 机械生物学
背景情况:
- 是的相关蛋白 (YAP) 是细胞生长和分化的关键调节者,对机械线索做出反应.
- 以前的研究集中在YAP对静态机械刺激的反应上,比如基板刚性.
- 介质干细胞 (MSC) 对于骨再生至关重要,它们的骨质分化受到机械力量的影响.
研究的目的:
- 调查动态机械负荷,特别是循环拉伸,如何影响MSC中的YAP机械感知.
- 在动态机械条件下确定YAP在MSC骨质分化中介作用.
- 阐明涉及这一过程的潜在分子机制,包括Hippo路径和ROCK-F-actin级联.
主要方法:
- 在MSC中进行循环机械拉伸 (10%应变,1Hz).
- 评估了YAP的核进口,酸化 (S127,S397) 和LATS酸化.
- 评估了骨质转录和分化,有或没有YAPsiRNA或ROCK抑制剂 (Y27632).
- 分析了F-actin形成,以了解细胞骨的作用.
主要成果:
- 循环拉伸诱导了MSC中的YAP核进口,通过抑制S127和S397的YAP酸化.
- 伸展治疗降低了LATS酸化,表明Hippo路径调节.
- 循环拉伸促进了MSC骨质性转录和分化,这种效应被YAPsiRNA减弱.
- 在拉伸下,YAP核运输和MSC骨质生成被ROCK抑制剂Y27632废除,涉及ROCK-F-actin通路.
结论:
- 动态机械拉伸是YAP介导的MSC骨质转录和分化的一个强有力的刺激.
- ROCK-F-actin级联在调解YAP对MSC动态机械负荷的反应中发挥着至关重要的作用.
- 这些发现为使用动态机械负荷来增强MSC再生能力的骨组织工程策略提供了洞察力.
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