Gardinier Joseph D, Mohamed Fatma, Kohn David H
Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, USA.
Oral Health Sciences Program, University of Michigan, Ann Arbor, MI, USA.
J Bone Miner Res. 2015 Jun;30(6):1053-63. doi: 10.1002/jbmr.2432.
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 parathyroid hormone (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); the second aim was to determine whether 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 twofold 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 platelike structure, which was inhibited with PTH(7-34) during exercise. Changes in structural-level 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-level 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 dynamic loading, but also PTH release, and that PTH signaling contributes differently at the structural and tissue levels.
增强骨骼的结构完整性可降低骨折风险以及晚年患骨质疏松症的几率。运动能够提升骨骼的力学性能，而这种提升通常归因于运动过程中产生的动态负荷。然而，运动过程中全身甲状旁腺激素（PTH）水平的升高使人有理由推测，PTH信号传导也会调节骨骼对运动的适应性。因此，本研究的首要目的是通过用PTH(7 - 34)抑制PTH信号传导来确定PTH信号传导对运动期间骨骼适应性的影响；第二个目的是确定在运动期间用PTH(1 - 34)提高PTH水平是否能增强骨骼适应性。在跑步机上单次跑步30分钟后，小鼠的全身PTH水平增加了两倍。在相同的运动方案下，连续21天运动并给予PTH(7 - 34)、PTH(1 - 34)或赋形剂后，评估PTH信号传导对小鼠运动期间骨骼适应性的影响。单独运动导致小梁骨体积显著增加，并适应更扁平的结构，而在运动期间用PTH(7 - 34)可抑制这种变化。运动期间结构水平和组织水平的力学性能发生了变化，而皮质骨几何形状没有显著变化。运动期间抑制PTH信号传导减弱了结构水平力学性能的变化，但对组织水平性能没有影响。在运动期间用PTH(1 - 34)增强PTH信号传导增加了小梁骨和皮质骨体积，但与单独运动相比，对结构水平和组织水平的力学性能影响较小。我们的研究首次表明，运动期间的骨骼适应性不仅是动态负荷的作用，也是PTH释放的作用，并且PTH信号传导在结构和组织水平上的作用有所不同。
