Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, London, UK.
Osteoporos Int. 2012 Apr;23(4):1225-34. doi: 10.1007/s00198-011-1656-4. Epub 2011 May 15.
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.
在小鼠胫骨中，骨细胞中骨硬化蛋白的表达受加载和去负荷的调节，但与引起的峰值应变相比，它与随后的局部成骨更为密切相关。
本研究的目的是评估与加载相关的骨细胞骨硬化蛋白表达变化、局部应变幅度以及局部骨形成/重塑之间的关系。
19 周龄雌性 C57BL/6 小鼠的右侧胫骨接受非侵入性、动态轴向加载和/或坐骨神经切断术诱导的去负荷。通过免疫组织化学评估骨细胞的骨硬化蛋白状态，通过微计算机断层扫描评估骨量变化，通过组织形态计量学评估新骨形成，通过应变计和有限元分析评估加载引起的应变。
在胫骨骨干的皮质骨中，加载在近端和远端产生相似峰值大小的应变。在近端，骨硬化蛋白阳性的骨细胞减少，新骨形成增加。在远端，既没有骨硬化蛋白阳性的骨细胞减少，也没有成骨增加。在近端次级松质骨的小梁骨中，加载减少了骨硬化蛋白阳性的骨细胞并增加了骨体积。在初级松质骨中则没有。在所有四个部位，去负荷都会增加骨硬化蛋白阳性的骨细胞并减少骨量。加载使近端皮质和次级松质骨中的骨硬化蛋白上调逆转至低于基线水平。
在小鼠胫骨中，与加载相关的骨细胞中骨硬化蛋白的下调与新骨形成受刺激的区域相关，而不是与产生的高峰值应变相关。涉及的机制尚不清楚，但可能与峰值表面应变不能准确反映与应变相关的成骨刺激有关，或者骨硬化蛋白的调节发生在足以区分局部成骨和非成骨反应的信号处理之后。
