PTH signaling mediates perilacunar remodeling during exercise
PTH signaling mediates perilacunar remodeling during exercise
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DOI：
10.1016/j.matbio.2016.02.010
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发表时间：
2016-05-01
期刊：
影响因子：
6.9
通讯作者：
Kohn, David H.
中科院分区：
文献类型：
--
作者：
Gardinier, Joseph D.;Al-Omaishi, Salem;Kohn, David H.
机械负荷和运动过程中内源性甲状旁腺激素（PTH）的释放促进了骨的适应。然而，目前尚不清楚运动和PTH如何影响骨的组成，以及运动和PTH介导的组成变化如何影响骨的机械性能。因此，本研究的主要目的是建立运动后骨细胞的骨皮质骨的月旁区域内的组成变化，并评估内源性PTH信号传导对这种月旁适应的影响。使用拉曼光谱、扫描电子显微镜（SEM）和能量色散X射线光谱（EDS）来评估暴露于跑步机跑步3周的19周龄雄性小鼠的胫骨内的各个陷窝周围的组织组成。作为运动的结果，与久坐的对照组相比，在骨陷窝周围区域内（骨陷窝壁的0-5 μ m内）的组织具有较低的矿物质-基质比（MMR）。此外，运动还增加了在周围和非周围区域（5-10 pm和10-15 pm的腔隙壁）的碳酸盐/磷酸盐比率（CPR）。胫骨屈服后工作与骨关节腔周围MMR呈显著负相关。用PTH（7-34）抑制PTH活性表明，运动期间的骨关节腔重塑依赖于对内源性PTH的细胞应答。在运动过程中，骨细胞对内源性PTH的反应的特征在于SOST表达的显著减少和FGF-23表达的显著增加。由于FGF-23表达导致的磷酸盐水平的潜在降低可以解释碳酸盐取代的增加。总的来说，这是第一项证明组织组成的适应性位于单个骨细胞周围的研究，可能有助于运动期间整个骨力学的变化，并且运动期间的PTH信号传导有助于这些适应性。(C)© 2016 Elsevier B. V.版权所有。
Mechanical loading and release of endogenous parathyroid hormone (PTH) during exercise facilitate the adaptation of bone. However, it remains unclear how exercise and PTH influence the composition of bone and how exercise and PTH-mediated compositional changes influence the mechanical properties of bone. Thus, the primary purpose of this study was to establish compositional changes within osteocytes' perilacunar region of cortical bone following exercise, and evaluate the influence of endogenous PTH signaling on this perilacunar adaptation. Raman spectroscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS) were used to evaluate tissue composition surrounding individual lacuna within the tibia of 19 week old male mice exposed to treadmill running for 3 weeks. As a result of exercise, tissue within the perilacunar region (within 0-5 pm of the lacuna wall) had a lower mineral-to-matrix ratio (MMR) compared to sedentary controls. In addition, exercise also increased the carbonate-to-phosphate ratio (CPR) across both perilacunar and non-perilacunar regions (5-10 pm and 10-15 pm from the lacuna walls). Tibial post-yield work had a significant negative correlation with perilacunar MMR. Inhibition of PTH activity with PTH(7-34) demonstrated that perilacunar remodeling during exercise was dependent on the cellular response to endogenous PTH. The osteocytes' response to endogenous PTH during exercise was characterized by a significant reduction in SOST expression and significant increase in FGF-23 expression. The potential reduction in phosphate levels due to FGF-23 expression may explain the increase in carbonate substitution. Overall, this is the first study to demonstrate that adaptation in tissue composition is localized around individual osteocytes, may contribute to the changes in whole bone mechanics during exercise, and that PTH signaling during exercise contributes to these adaptations. (C) 2016 Elsevier B.V. All rights reserved.