PTH Signaling During Exercise Contributes to Bone Adaptation.
PTH Signaling During Exercise Contributes to Bone Adaptation.
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运动过程中的PTH信号传导有助于骨适应。
DOI：
10.1002/jbmr.2432
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Kohn DH
中科院分区：
文献类型：
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作者：
Gardinier JD;Mohamed F;Kohn DH
改善骨骼的结构完整性可以降低骨折风险和在晚年患上骨质疏松症。运动可以增加骨骼的力学性能，这种增加通常被归因于运动过程中产生的动态负荷。然而，运动过程中全身性甲状旁腺素水平的增加提供了假设的理由，即甲状旁腺素信号也调节对运动的骨适应。因此，本研究的第一个目的是通过用PTH(7-34)抑制PTH信号来确定运动中PTH信号对骨适应的影响，第二个目的是确定在运动中用PTH(1-34)增加PTH水平是否可以增强骨适应。在跑步机上跑步30分钟后，小鼠全身甲状旁腺素水平增加了两倍。在相同的运动方案下，在连续21天的运动和甲状旁腺素(7-34)、甲状旁腺素(1-34)或赋形剂治疗后，评估甲状旁腺素信号对运动中骨适应的影响。单独运动导致骨小梁体积显著增加，并适应更多的板状结构，这在运动中被PTH(7-34)抑制。在运动过程中，结构和组织水平的力学性能发生变化，而皮质骨几何形状没有明显变化。在运动过程中抑制甲状旁腺素信号可以减弱结构水平的机械性能的变化，但不能减轻组织水平的性能变化。与单独运动相比，PTH(1-34)在运动过程中增强的PTH信号增加了骨小梁和皮质骨的体积，但对结构和组织水平的力学性能几乎没有影响。我们的研究首次证明运动过程中的骨适应不仅是动态负荷的函数，而且是PTH释放的函数，并且PTH信号在结构和组织水平上的作用是不同的。
Improving the structural integrity of bone reduces fracture risk and development of osteoporosis later in life. Exercise can increase the mechanical properties of bone, and this increase is often attributed to the dynamic loading created during exercise. However, the increase in systemic PTH levels during exercise gives reason to hypothesize that PTH signaling also regulates bone adaptation in response to exercise. Therefore, the first aim of this study was to establish the impact PTH signaling has on bone adaptation during exercise by inhibiting PTH signaling with PTH(7-34) and the second aim was to determine if increasing PTH levels during exercise with PTH(1-34) can augment bone adaptation. Thirty minutes after a single bout of running on a treadmill, mice exhibited a two-fold increase in systemic PTH levels. Under the same exercise regimen, the influence of PTH signaling on bone adaptation during exercise was then evaluated in mice after 21 consecutive days of exercise and treatment with PTH(7-34), PTH(1-34), or vehicle. Exercise alone caused a significant increase in trabecular bone volume with adaptation to a more plate-like structure, which was inhibited with PTH(7-34) during exercise. Changes in structural and tissue-level mechanical properties during exercise occurred in the absence of significant changes to cortical bone geometry. Inhibition of PTH signaling during exercise attenuated the changes in structural-level mechanical properties, but not tissue-level properties. Enhanced PTH signaling during exercise with PTH(1-34) increased trabecular and cortical bone volume, but had little effect on the structural and tissue-level mechanical properties compared to exercise alone. Our study is the first to demonstrate that bone adaptation during exercise is not only a function of the dynamic loading, but also PTH release, and that PTH signaling contributes differently at the structural and tissue-levels.