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使用CRISPR/Cas9介导的光记者小鼠阐明TRAP活动的机械分子动力学

Dilara Yılmaz¹, Francisco C Marques¹, Yannick Fischer¹

¹Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.

|July 18, 2024

概括

耐酸酸酶 (TRAP) 对于骨质细胞在骨重塑中的功能至关重要. 这项研究发现,TRAP缺乏在体外影响骨,但在体内不影响再吸收或机械敏感性.

科学领域:

骨生物学骨生物学骨生物学
骨生理学骨生理学
细胞机械传导细胞机械传导

背景情况:

骨质细胞通过感知机械线索来调节骨重塑.
耐酸酸酶 (TRAP) 在骨质细胞机械敏感性中的确切作用尚未完全理解.

研究的目的:

研究TRAP (Acp5) 在骨质细胞机械敏感性和骨重塑中的功能.
阐明将TRAP活性与骨中的机械适应联系起来的分子机制.

主要方法:

产生CRISPR/Cas9记者小鼠 (BCR^Ibsp/Acp5) 与光TRAP缺乏骨质细胞.
在机械驱动的椎骨改造过程中评估骨质细胞活性.
在体外再吸收试验,RNA测序,血清CTX测量和体内机械负荷.

主要成果:

缺少TRAP的骨质结晶体在体外表现出骨再吸收受损,但在体内没有.
在缺乏TRAP的骨质细胞中,RNA测序没有显示关键骨质细胞基因 (Ctsk,Mmp9,Calcr) 的显著变化.
在TRAP缺乏和野生类型小鼠之间,状骨重塑的机制调节类似.

结论:

在骨质细胞机械敏感性和体内骨再吸收能力方面,TRAP的作用不如以前所认为那么重要.
TRAP活动动态很复杂,并且不仅仅是在骨重塑过程中决定骨质细胞机械感应.

关键词:

骨改造骨改造骨改造骨改造在CRISPR/Cas9中介的记者小鼠中.光骨质细胞和骨质母细胞.在生物体内加载.机械敏感性机械敏感性微型计算机断层扫描 (micro-computed tomography) 是一种微型计算机断层扫描.微有限元素分析.在TRAP中存在缺陷.脊椎骨的骨头改造脊椎骨的骨头改造

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