Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered.
Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered.
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DOI：
10.1007/s00198-011-1656-4
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发表时间：
2012-04
影响因子：
4
通讯作者：
Price, J. S.
中科院分区：
文献类型：
--
作者：
Moustafa, A.;Sugiyama, T.;Prasad, J.;Zaman, G.;Gross, T. S.;Lanyon, L. E.;Price, J. S.
骨细胞硬化蛋白在小鼠胫骨中受负荷和废用的调节，但与随后的局部成骨比产生的峰值应变更密切相关。本研究的目的是评估骨细胞sclerostin表达的负荷相关变化、局部应变幅度和局部骨建模/重塑之间的关系。对19周龄雌性C57 BL/6小鼠的右胫骨进行非侵入性动态轴向负荷和/或坐骨神经切除术诱导的废用。骨细胞的sclerostin状态进行了化学评价，骨质量的变化，通过显微计算机断层扫描，新骨形成的组织形态计量学，和负载引起的应变仪和有限元分析。在胫骨干的皮质骨中，载荷产生了近端和远端相似峰值的应变。近端，硬化蛋白阳性骨细胞减少，新骨形成增加。在远端，硬化蛋白阳性骨细胞既没有减少，也没有增加骨生成。在近端次级松质骨的松质骨中，负荷减少了硬化蛋白阳性骨细胞，增加了骨体积。也没有发生在初级海绵体。废用增加硬化蛋白阳性骨细胞和减少骨体积在所有四个网站。负荷逆转了这种sclerostin上调至低于近端皮质和继发性海绵体中基线的水平。小鼠胫骨骨细胞中负荷相关的硬化蛋白下调优先与新骨形成被刺激的区域相关，而不是产生高峰应变的区域。所涉及的机制尚不清楚，但可能与峰表面应变不准确反映应变相关的成骨刺激或sclerostin调节后发生足够的信号处理，以区分局部成骨和非成骨反应。
Osteocyte sclerostin is regulated by loading and disuse in mouse tibiae but is more closely related to subsequent local osteogenesis than the peak strains engendered. The purpose of this study was to assess the relationship between loading-related change in osteocyte sclerostin expression, local strain magnitude, and local bone modeling/remodeling. The right tibiae of 19-week-old female C57BL/6 mice were subjected to non-invasive, dynamic axial loading and/or to sciatic neurectomy-induced disuse. The sclerostin status of osteocytes was evaluated immunohistochemically, changes in bone mass by micro-computed tomography, new bone formation by histomorphometry, and loading-induced strain by strain gauges and finite element analysis. In cortical bone of the tibial shaft, loading engendered strains of similar peak magnitude proximally and distally. Proximally, sclerostin-positive osteocytes decreased and new bone formation increased. Distally, there was neither decrease in sclerostin-positive osteocytes nor increased osteogenesis. In trabecular bone of the proximal secondary spongiosa, loading decreased sclerostin-positive osteocytes and increased bone volume. Neither occurred in the primary spongiosa. Disuse increased sclerostin-positive osteocytes and decreased bone volume at all four sites. Loading reversed this sclerostin upregulation to a level below baseline in the proximal cortex and secondary spongiosa. Loading-related sclerostin downregulation in osteocytes of the mouse tibia is associated preferentially with regions where new bone formation is stimulated rather than where high peak strains are engendered. The mechanisms involved remain unclear, but could relate to peak surface strains not accurately reflecting the strain-related osteogenic stimulus or that sclerostin regulation occurs after sufficient signal processing to distinguish between local osteogenic and non-osteogenic responses.
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影响因子：
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作者：
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通讯作者：
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