Variation in within-bone stiffness measured by nanoindentation in mice bred for high levels of voluntary wheel running.

Variation in within-bone stiffness measured by nanoindentation in mice bred for high levels of voluntary wheel running.
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通过纳米压痕测量高水平自愿轮跑饲养小鼠的骨内硬度变化。

DOI:
10.1111/j.1469-7580.2009.01175.x
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发表时间:
2010
期刊:
影响因子:
2.4
通讯作者:
GarlandJr,T
GarlandJr,T
中科院分区:
医学3区
文献类型:
--
作者:
Middleton,KevinM;Goldstein,BethD;Guduru,PradeepR;Waters,JulieF;Kelly,ScottA;Swartz,SharonM;GarlandJr,T

文献摘要

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骨的层次结构涉及材料组分的微观组织和相互作用,是宏观力学的关键决定因素。全骨形态的变化响应于个体基因的作用、生命过程中的生理负荷或进化过程,可能伴随着潜在矿化或结构的改变。在这里,我们使用纳米压痕法精确测量了小鼠股骨中段的压缩刚度,这些小鼠经历了37代的选择性繁殖,以获得高水平的自愿轮跑(HR)。将一半来自HR系和一半来自非选择的对照(C)系的小鼠(总共n=48)分成两个实验组,一个实验组具有13-14周的使用转轮的通道,另一个实验组在没有转轮的情况下饲养(每组n= 12)。   在实验结束时,测量基于大体和微计算机断层扫描(μCT)的形态测量特征,并分别估计股骨皮质的四个解剖象限(前、后、外侧和内侧)的折合弹性模量(Er)。双因素混合模型协方差分析(ancova)显示,体重是所有形态测量学特征的高度显著预测因子,μCT水平的结构变化比传统的全骨形态测量学更明显。线型(HR vs. C)和小肌肉表型(由孟德尔隐性等位基因引起,特征为腓肠肌复合体质量减少约50%)的存在是股骨皮质横截面解剖结构的重要预测因素。通过纳米压痕获得的折合模量的测量在单个象限内是可重复的,并且足够灵敏以检测个体间差异。虽然我们发现线型(HR vs. C)或体力活动(有轮子的vs.无轮子的)对平均硬度没有显著影响,但前象限和后象限的硬度显著高于(P<0.0001)内侧象限和外侧象限(分别为32.67和33.09 GPa vs. 29.78和30.46 GPa)。   我们的研究结果没有显着差异的压缩刚度的前,后象限同意以前的结果,小鼠,但不同于那些大型哺乳动物。将这些结果与正在进行的对这些小鼠的研究中的其他结果相结合,我们假设雌性HR小鼠的骨骼可能对慢性运动的影响不太敏感,这是由于循环瘦素水平降低和内源性大麻素信号转导的潜在改变。
The hierarchical structure of bone, involving micro‐scale organization and interaction of material components, is a critical determinant of macro‐scale mechanics. Changes in whole‐bone morphology in response to the actions of individual genes, physiological loading during life, or evolutionary processes, may be accompanied by alterations in underlying mineralization or architecture. Here, we used nanoindentation to precisely measure compressive stiffness in the femoral mid‐diaphysis of mice that had experienced 37 generations of selective breeding for high levels of voluntary wheel running (HR). Mice (n= 48 total), half from HR lines and half from non‐selected control (C) lines, were divided into two experimental groups, one with 13–14 weeks of access to a running wheel and one housed without wheels (n= 12 in each group). At the end of the experiment, gross and micro‐computed tomography (μCT)‐based morphometric traits were measured, and reduced elastic modulus (Er) was estimated separately for four anatomical quadrants of the femoral cortex: anterior, posterior, lateral, and medial. Two‐way, mixed‐model analysis of covariance (ancova) showed that body mass was a highly significant predictor of all morphometric traits and that structural change is more apparent at the μCT level than in conventional morphometrics of whole bones. Both linetype (HR vs. C) and presence of the mini‐muscle phenotype (caused by a Mendelian recessive allele and characterized by a ∼50% reduction in mass of the gastrocnemius muscle complex) were significant predictors of femoral cortical cross‐sectional anatomy. Measurement of reduced modulus obtained by nanoindentation was repeatable within a single quadrant and sensitive enough to detect inter‐individual differences. Although we found no significant effects of linetype (HR vs. C) or physical activity (wheel vs. no wheel) on mean stiffness, anterior and posterior quadrants were significantly stiffer (P< 0.0001) than medial and lateral quadrants (32.67 and 33.09 GPa vs. 29.78 and 30.46 GPa, respectively). Our findings of no significant difference in compressive stiffness in the anterior and posterior quadrants agree with previous results for mice, but differ from those for large mammals. Integrating these results with others from ongoing research on these mice, we hypothesize that the skeletons of female HR mice may be less sensitive to the effects of chronic exercise, due to decreased circulating leptin levels and potentially altered endocannabinoid signaling.