Trabecular and Cortical Bone of Growing C3H Mice Is Highly Responsive to the Removal of Weightbearing.
Trabecular and Cortical Bone of Growing C3H Mice Is Highly Responsive to the Removal of Weightbearing.
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DOI：
10.1371/journal.pone.0156222
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Judex S
中科院分区：
文献类型：
--
作者：
Li B;Sankaran JS;Judex S
遗传组成强烈影响骨骼对承重损失的敏感性，一些近交系小鼠品系经历大量的骨损失，而另一些则以小得多的速率损失骨。在成年初期，雌性近交系C3 H/HeJ（C3 H）小鼠在很大程度上抵抗由卸载引起的分解代谢压力。在这里，我们测试了对卸载的抑郁反应是否是C3 H基因组成所固有的，或者年轻的年龄是否有助于对卸载产生强大的骨骼反应。对9周龄的未成熟雌性C3 H小鼠进行3周的后肢卸载（HLU，n = 12）或作为正常基线对照（BC，n = 10）或年龄匹配的对照（AC，n = 12）。在所有小鼠中，采用μCT、组织形态计量学和组织学评估股骨的皮质和小梁结构以及骨形成和吸收水平。用流式细胞术测定骨髓祖细胞群的变化。卸载21天后，HLU小鼠股骨远端的骨小梁比正常年龄匹配的对照组少52%。与基线对照组相比，HLU小鼠的骨小梁形成率（BFR/BS）比年龄匹配的对照组低40%，反映了骨小梁组织的损失。两组间发生骨吸收的表面无显著差异。在骨干中段，HLU抑制皮质骨生长，导致骨面积比年龄匹配的对照组减少14%。与AC相比，HLU小鼠的BFR/BS在皮质内表面低53%，在骨干中段的骨膜表面低49%。富集的骨祖细胞群（OPC）包括HLU小鼠中2%的骨髓干细胞，与AC组中3%的OPC显著不同。这些数据表明，在积极增长的C3 H小鼠的骨组织丢失迅速，或未能增长，在功能性负重的去除，在以前证明在女性年轻的成年C3 H小鼠的微不足道的反应相反。因此，C3 H小鼠品系对机械信号丢失的低敏感性在幼年时并不明显，因此该性状不反映该品系整个生命周期的遗传调控。这些结果强调了年龄在调节遗传学在协调骨对卸载的反应中的贡献中的重要性，并且年轻成年C3 H小鼠对承重损失的骨骼无反应性不是遗传上的硬连线。
Genetic make-up strongly influences the skeleton’s susceptibility to the loss of weight bearing with some inbred mouse strains experiencing great amounts of bone loss while others lose bone at much smaller rates. At young adulthood, female inbred C3H/HeJ (C3H) mice are largely resistant to catabolic pressure induced by unloading. Here, we tested whether the depressed responsivity to unloading is inherent to the C3H genetic make-up or whether a younger age facilitates a robust skeletal response to unloading. Nine-week-old, skeletally immature, female C3H mice were subjected to 3wk of hindlimb unloading (HLU, n = 12) or served as normal baseline controls (BC, n = 10) or age-matched controls (AC, n = 12). In all mice, cortical and trabecular architecture of the femur, as well as levels of bone formation and resorption, were assessed with μCT, histomorphometry, and histology. Changes in bone marrow progenitor cell populations were determined with flow cytometry. Following 21d of unloading, HLU mice had 52% less trabecular bone in the distal femur than normal age-matched controls. Reflecting a loss of trabecular tissue compared to baseline controls, trabecular bone formation rates (BFR/BS) in HLU mice were 40% lower than in age-matched controls. Surfaces undergoing osteoclastic resorption were not significantly different between groups. In the mid-diaphysis, HLU inhibited cortical bone growth leading to 14% less bone area compared to age-matched controls. Compared to AC, BFR/BS of HLU mice were 53% lower at the endo-cortical surface and 49% lower at the periosteal surface of the mid-diaphysis. The enriched osteoprogenitor cell population (OPC) comprised 2% of the bone marrow stem cells in HLU mice, significantly different from 3% OPC in the AC group. These data show that bone tissue in actively growing C3H mice is lost rapidly, or fails to grow, during the removal of functional weight bearing—in contrast to the insignificant response previously demonstrated in female young adult C3H mice. Thus, the attributed low sensitivity of the C3H mouse strain to the loss of mechanical signals is not apparent at a young age and this trait therefore does not reflect a genetic regulation throughout the life span of this strain. These results highlight the significance of age in modulating the contribution of genetics in orchestrating bone’s response to unloading and that the skeletal unresponsiveness of young adult C3H mice to the loss of weight bearing is not genetically hard-wired.