Bone development and age-related bone loss in male C57BL/6J mice

Bone development and age-related bone loss in male C57BL/6J mice
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DOI:
10.1016/s8756-3282(03)00199-6
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发表时间:
2003-09-01
期刊:
影响因子:
4.1
通讯作者:
Simske, SJ
Simske, SJ
中科院分区:
医学2区
文献类型:
--
作者:
Ferguson, VL;Ayers, RA;Simske, SJ

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本研究的目的是观察雄性C57BL/6J小鼠长骨随生长和衰老的变化,并考虑该动物在II型骨质疏松症研究中的适用性。雄性C57BL/6J小鼠在4 ~ 104周龄(n = 9-15/组)。测量股骨和肱骨的长度,并进行力学测试(三点屈曲)和成分分析。将左侧股骨包埋,对骨干中部厚片进行形态学、形成指数和骨结构评估。在幼鼠中,快速生长的特征是骨骼大小、矿物质质量和机械性能的显著增加。成熟发生在12 - 42周龄,骨量和力学性能得以维持。从峰值水平来看,104周龄小鼠的全股骨质量(干质量和灰分质量分别为12.1%和18.6%)、矿化率(7.4%)、全骨刚度(29.2%)、骨折能(51.8%)和皮质厚度(20.1%)下降。从研究开始,表面形成的指数迅速下降。然而,骨膜周长和截面惯性矩在104周内继续增加,从而保持了结构特性。这弥补了由于矿化和硬度降低而导致的皮质变薄和脆性增加。老年小鼠中骨干的形状越来越不椭圆,20-50%大于或等于78周龄的股骨存在皮质内吸收和后续形成的证据。这一点。结合52周后出现过度皮质内吸收,提示骨形状和位置的正常调节机制发生改变,提示骨重塑。本研究中股骨骨干中段骨质流失的模式与II型骨质疏松症患者股骨颈皮质骨明显相似。因此,本研究表明,雄性C57BL/6J小鼠是研究内源性衰老相关骨质减少的一种新的合适模型,可能是研究II型骨质疏松症的有用模型。(C) 2003 Elsevier Inc.版权所有。
The objective of this study was to examine changes in the long bones of male C57BL/6J mice with growth and aging, and to consider the applicability of this animal for use in studying Type II osteoporosis. Male C57BL/6J mice were aged in our colony between 4 and 104 weeks (n = 9-15/group). The fight femur and humeri were measured for length and subjected to mechanical testing (3-point flexure) and compositional analysis. The left femurs were embedded and thick slices at the mid-diaphysis were assessed for morphology, formation indices, and bone structure. In young mice, rapid growth was marked by substantial increases in bone size, mineral mass, and mechanical properties. Maturity occurred between 12 and 42 weeks of age with the maintenance of bone mass and mechanical properties. From peak levels, mice aged for 104 weeks experienced decreased whole femur mass (12.1 and 18.6% for dry and ash mass, respectively), percentage mineralization (7.4%), diminished whole bone stiffness (29.2%), energy to fracture (51.8%), and decreased cortical thickness (20.1%). Indices of surface-based formation decreased rapidly from the onset of the study. However, the periosteal perimeter and, consequently, the cross-sectional moments of inertia continued to increase through 104 weeks, thus maintaining structural properties. This compensated for cortical thinning and increased brittleness due to decreased mineralization and stiffness. The shape of the mid-diaphysis became increasingly less elliptical in aged mice, and endocortical resorption and evidence of subsequent formation were present in 20-50% of femurs aged greater than or equal to78 weeks. This. combined with the appearance of excessive endocortical resorption after 52 weeks, indicated a shift in normal mechanisms regulating bone shape and location, and was suggestive of remodeling. The pattern of bone loss at the femoral mid-diaphysis in this study is markedly similar to that seen in cortical bone in the human femoral neck in Type II osteoporosis. This study has thus demonstrated that the male C57BL/6J mouse is a novel and appropriate model for use in studying endogenous, aging-related osteopenia and may be a useful model for the study of Type II osteoporosis. (C) 2003 Elsevier Inc. All rights reserved.