机械反应干细胞在再生中获得神经的命运
Ryan C Ransom1,2, Ava C Carter3, Ankit Salhotra1,2
1Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|October 26, 2018
概括
机械力量触发骨干细胞通过重新激活发育基因程序来再生骨. 抑制焦粘附激酶 (FAK) 阻断了这一关键的骨再生过程.
科学领域:
- 骨生物学
- 复原医学
- 机械生物学
背景情况:
- 成人组织的再生依赖于对刺激的干细胞.
- 了解机械力量如何影响骨干细胞的再生至关重要.
- mandibular 干扰骨质生成提供了一个研究骨再生的模型.
研究的目的:
- 研究机械刺激在骨干干细胞中介再生中的作用.
- 阐明骨干干细胞中机械传导的分子机制.
- 在下干扰骨质生成过程中确定关键信号通路.
主要方法:
- 开发一个基因可剖析的小鼠模型用于下分心骨质生成.
- 克隆分析以追踪新形成的骨的起源.
- 染色体和转录分析以分析干细胞活动.
- 对焦粘附激酶 (FAK) 途径的药理抑制.
主要成果:
- 在分心骨质发生过程中,新形成的骨是从居住的骨干细胞中克隆衍生出来的.
- 骨干细胞在再生过程中激活焦粘附激酶 (FAK) 信号通路.
- 抑制FAK完全消除了新的骨形成.
- 通过FAK介导的机械转移重新激活了原始神经细胞的基因调节程序和逆转移体.
结论:
- 骨干干细胞在再生过程中恢复到发育状态,由FAK信号提供.
- 这种回归原始状态是成年骨组织基于干细胞的强大再生的基础.
- 向FAK信号可能提供增强骨再生的治疗策略.
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