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在活体中,Prrx1驱动的LINC复合体中断减少了骨体沉积,但在自愿轮子运行后,骨质并没有降低

Scott Birks¹, Sean Howard², Christian S Wright³

¹Boise State University, Micron School of Materials Science and Engineering.

bioRxiv : the preprint server for biology

|October 4, 2023

概括

破坏骨前细胞中核骨和细胞骨 (LINC) 复合体的链接器,可以防止运动诱导的骨形成. 这表明LINC复合体对于骨适应机械负荷至关重要.

科学领域:

细胞生物学细胞生物学
骨生物学骨生物学
生物物理学的生物物理.

背景情况:

核骨和细胞骨的连接器 (LINC) 综合体将细胞核与细胞骨连接起来,影响细胞过程和机械传导.
虽然LINC在骨前代细胞机械传导中的作用是已知的,但其在骨形成中的活体功能却不太了解.
了解LINC复杂机制对于骨发育和适应研究至关重要.

研究的目的:

研究LINC复合体在骨干发育和运动诱导的骨积累期间在骨干前代细胞中的活体作用.
建立和利用一种新的小鼠模型,用于细胞特异性的LINC复合体破坏.

主要方法:

使用转基因 Prx-Cre 和 floxed Tg ((CAG-LacZ/EGFP-KASH2) 鼠标生成了一个 Prrx1 (((+) 细胞特异的 LINC 干扰模型.
该模型破坏了内源性纳斯-太阳结合,以主导负的方式将纳斯与核外断开.
在体育炼干预后,评估骨质和脂肪生成潜力in vitro,并分析骨质,微架构和机械特性in vivo.

主要成果:

与对照组相比,Prx驱动的LINC干扰 (PDLD) 细胞在骨质生成或脂肪生成潜力上没有差异in vitro.
与静止控制组相比,PDLD动物在8周后没有表现出骨质质量变化.
在PDLD动物中,经过6周的运动干预后,运动诱导的骨体积和表面的增加被废除了,没有观察到其他微观架构或机械变化.

结论:

在没有机械负荷的情况下,Prrx1(+) 细胞特异性的LINC中断不会影响基底骨的形成或质量.
骨前代细胞中的LINC复合体对于调解运动诱导的骨积累至关重要.
这些发现突出了LINC介导的机械传导在骨适应体力活动中的关键作用.

关键词:

骨头骨头骨头骨头在 LINC 找 LINC.机械信号机械信号机械生物学机械生物学中介细胞干细胞中介细胞干细胞配对相关的同源盒基因-1 (Prrx1)

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