通过YAP-CCN-Src信号轴,Piezo1介导的机械传导控制骨细胞成熟和树发育
Yizhong Jenny Hu1, Xinchen Wu1, Fuhua Wang1
1Department of Developmental Biology, Harvard School of Dental Medicine; Harvard Stem Cell Institute, Boston, MA, USA.
Nature communications
|November 28, 2025
概括
机械力是由骨细胞,关键骨细胞感知到的. 皮埃佐1蛋白对骨细胞状物形成和骨健康至关重要,其损失会损害这些功能.
科学领域:
- 骨生物学 骨生物学 骨生物学
- 机械生物学 机械生物学
- 细胞机械传导 细胞机械传导
背景情况:
- 机械力量调节骨质稳定,骨细胞作为关键机械传感器.
- 骨细胞树突对于感知机械刺激和调解骨重塑至关重要.
- 控制骨细胞成熟和树发育的分子途径尚未完全理解.
研究的目的:
- 研究Piezo1在骨细胞分化和树形成中的作用.
- 阐明将Piezo1与骨细胞功能和骨质量联系起来的分子机制.
- 确定增强骨细胞树突网络的潜在治疗点.
主要方法:
- 使用Piezo1淘汰赛小鼠模型 (晚期骨质母细胞和骨质细胞).
- 评估骨质量,骨细胞分化和树突网络形态.
- 分析了YAP,Wnt/β-catenin,CCN1/2和Src的信号通路.
- 研究了间歇性YAP激活和CCN1/2过度表达的影响.
主要成果:
- 骨细胞中皮埃佐1缺乏导致骨质量减少和骨细胞分化受损.
- 丢失Piezo1导致树突数量,长度和网络复杂性下降.
- 这些缺陷与减少YAP活动和激活Wnt/β-catenin信号传递有关.
- YAP激活部分恢复树突和骨表型;CCN1/2过度表达通过Src激活和YAP反挽救了缺陷.
结论:
- Piezo1对于骨细胞成熟和功能性树突网络的形成至关重要.
- 该Piezo1-YAP-CCN1/2-Src信号轴对于骨细胞机械转导和骨质稳定至关重要.
- 针对这种途径为骨功能受损的骨细胞疾病提供了潜在的治疗策略.
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