Mechanical loading regulates organization of the actin cytoskeleton and column formation in postnatal growth plate.
Mechanical loading regulates organization of the actin cytoskeleton and column formation in postnatal growth plate.
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DOI：
10.1091/mbc.e17-02-0084
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发表时间：
2017-07-07
影响因子：
3.3
通讯作者：
Serra R
中科院分区：
文献类型：
--
作者：
Killion CH;Mitchell EH;Duke CG;Serra R
骨骼的纵向生长发生在生长板处，其中软骨细胞排列成允许定向生长的柱。软骨细胞上的机械负荷和力调节出生后生长板的组织和肢体长度。骨骼的纵向生长发生在生长板处，其中软骨细胞排列成允许定向生长的柱。关于控制软骨细胞形成柱的能力的机制知之甚少。我们假设软骨细胞的机械负荷和由此产生的力在活跃生长过程中对于适当的生长板发育和肢体长度是必要的。为了验证这一假设，我们创建了一个小鼠模型，在出生后第 8 天横断一侧后肢的部分坐骨神经，导致该肢体瘫痪。术后 6 周和 12 周时，后肢的骨矿物质密度明显低于对侧对照，证实负荷减轻。术后 8 周和 14 周，胫骨明显短于对照组。瘫痪的生长板显示柱组织受到破坏，柱更少更短。偏光显微镜显示生长板中胶原纤维组织的变化。此外，生长板软骨细胞中肌动蛋白细胞骨架的组织被破坏。我们得出的结论是，生长板内软骨细胞上的机械负荷和力调节长骨的出生后发育。
Longitudinal growth of bones occurs at the growth plates, where chondrocytes align into columns that allow directional growth. Mechanical load and force on chondrocytes regulate the organization of the postnatal growth plate and limb length. Longitudinal growth of bones occurs at the growth plates where chondrocytes align into columns that allow directional growth. Little is known about the mechanisms controlling the ability of chondrocytes to form columns. We hypothesize that mechanical load and the resulting force on chondrocytes are necessary during active growth for proper growth plate development and limb length. To test this hypothesis, we created a mouse model in which a portion of the sciatic nerve from one hind limb was transected at postnatal day 8 to cause paralysis to that limb. At 6 and 12 wk postsurgery, the hind limb had significantly less bone mineral density than contralateral controls, confirming reduced load. At 8 and 14 wk postsurgery, tibiae were significantly shorter than controls. The paralyzed growth plate showed disruptions to column organization, with fewer and shorter columns. Polarized light microscopy indicated alterations in collagen fiber organization in the growth plate. Furthermore, organization of the actin cytoskeleton in growth plate chondrocytes was disrupted. We conclude that mechanical load and force on chondrocytes within the growth plate regulate postnatal development of the long bones.