Examining the influence of PTH(1-34) on tissue strength and composition.

Examining the influence of PTH(1-34) on tissue strength and composition.
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DOI:
10.1016/j.bone.2018.09.019
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发表时间:
2018-12
期刊:
影响因子:
4.1
通讯作者:
Kohn DH
Kohn DH
中科院分区:
医学2区
文献类型:
--
作者:
Gardinier JD;Al-Omaishi S;Rostami N;Morris MD;Kohn DH

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骨陷窝-小管系统是骨细胞嵌入整个皮质骨时产生和维持的通道网络。随着骨细胞改变其骨陷窝空间,局部组织组成和组织强度发生变化。虽然持续暴露于甲状旁腺激素(PTH)可以诱导适应在腔隙壁,间歇性甲状旁腺激素治疗的影响,对周围的适应仍然不清楚。因此,本研究的主要目的是确定间歇性PTH(1-34)治疗如何影响组织成分变化方面的骨适应。我们假设,PTH(1-34)后组织成分的局部变化与组织强度的相应增加和整个骨水平的微损伤抵抗力相关。每天用PTH(1-34)或媒介物处理成年雄性C57 BL/6 J小鼠,持续3周。针对PTH(1-34),拉曼光谱显示整个组织的碳酸盐/磷酸盐比率和结晶度显著降低,而矿物质/基质比率仅在月旁区域显示显著降低。在很大程度上解释了相应的组织强度的增加,而在骨内膜和骨膜的新组织添加的程度没有产生任何显着的皮质面积或惯性矩的变化,将解释组织强度的增加。此外,疲劳测试显示,经过PTH(1-34)处理后,现有组织内的裂纹形成阻力更大。因此,骨关节斑周围组成的变化呈现出一种独特的机制,通过该机制,PTH(1-34)产生组织质量的局部差异,允许在负荷下耗散更多的能量,从而增加组织强度和抗微损伤性。此外,我们的研究结果表明PTH(1-34)通过产生更柔顺的组织来放大骨细胞的机械转导的潜力。总体而言,本研究表明,骨陷窝壁组织成分的变化有助于间歇性PTH(1-34)治疗后获得的皮质骨强度和抗疲劳性。
The lacunar-canaliculi system is a network of channels that is created and maintained by osteocytes as they are embedded throughout cortical bone. As osteocytes modify their lacuna space, the local tissue composition and tissue strength are subject to change. Although continual exposure to parathyroid hormone (PTH) can induce adaptation at the lacunar wall, the impact of intermittent PTH treatment on perilacunar adaptation remains unclear. Therefore, the primary objective of this study was to establish how intermittent PTH(1–34) treatment influences perilacunar adaptation with respect to changes in tissue composition. We hypothesized that local changes in tissue composition following PTH(1–34) are associated with corresponding gains in tissue strength and resistance to microdamage at the whole bone level. Adult male C57BL/6J mice were treated daily with PTH(1–34) or vehicle for 3 weeks. In response to PTH(1–34), Raman spectroscopy revealed a significant decrease in the carbonate-to-phosphate ratio and crystallinity across the entire tissue, while the mineral-to-matrix ratio demonstrated a significant decrease in just the perilacunar region. The shift in perilacunar composition largely explained the corresponding increase in tissue strength, while the degree of new tissue added at the endosteum and periosteum did not produce any significant changes in cortical area or moment of inertia that would explain the increase in tissue strength. Furthermore, fatigue testing revealed a greater resistance to crack formation within the existing tissue following PTH(1–34) treatment. As a result, the shift in perilacunar composition presents a unique mechanism by which PTH(1–34) produces localized differences in tissue quality that allow more energy to be dissipated under loading, thereby increasing tissue strength and resistance to microdamage. In addition, our findings demonstrate the potential for PTH(1–34) to amplify osteocytes’ mechanotransduction by producing a more compliant tissue. Overall, the present study demonstrates that changes in tissue composition localized at the lacuna wall contribute to the strength and fatigue resistance of cortical bone gained in response to intermittent PTH(1–34) treatment.
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期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
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