Gardinier Joseph D, Al-Omaishi Salam, Morris Michael D, Kohn David H
Bone and Joint Center, Henry Ford Hospital, Detroit, MI 48202, USA; Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Matrix Biol. 2016 May-Jul;52-54:162-175. doi: 10.1016/j.matbio.2016.02.010. Epub 2016 Feb 23.
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 19week old male mice exposed to treadmill running for 3weeks. As a result of exercise, tissue within the perilacunar region (within 0-5μm 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 (5-10μm and 10-15μm 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.
运动过程中内源性甲状旁腺激素（PTH）的机械负荷与释放有助于骨骼的适应性变化。然而，运动和PTH如何影响骨骼成分，以及运动和PTH介导的成分变化如何影响骨骼的力学性能，目前仍不清楚。因此，本研究的主要目的是确定运动后皮质骨骨细胞陷窝周围区域的成分变化，并评估内源性PTH信号对这种陷窝周围适应性变化的影响。采用拉曼光谱、扫描电子显微镜（SEM）和能量色散X射线光谱（EDS），对19周龄雄性小鼠进行3周跑步机跑步训练后胫骨中单个陷窝周围的组织成分进行评估。运动后，与久坐不动的对照组相比，陷窝周围区域（陷窝壁0 - 5μm范围内）的组织矿化与基质比（MMR）较低。此外，运动还增加了陷窝周围和非陷窝周围区域（距陷窝壁5 - 10μm和10 - 15μm）的碳酸盐与磷酸盐比（CPR）。胫骨屈服后功与陷窝周围MMR呈显著负相关。用PTH(7 - 34)抑制PTH活性表明，运动过程中的陷窝周围重塑依赖于细胞对内源性PTH的反应。运动过程中骨细胞对内源性PTH的反应特征为SOST表达显著降低，FGF - 23表达显著增加。FGF - 23表达导致的磷酸盐水平潜在降低可能解释了碳酸盐替代的增加。总体而言，这是第一项证明组织成分适应性变化定位于单个骨细胞周围、可能导致运动过程中全骨力学变化，且运动过程中PTH信号有助于这些适应性变化的研究。
