Variation in Bone Biomechanical Properties, Microstructure, and Density in BXH Recombinant Inbred Mice
作者:Charles H. Turner、Yeou-Fang Hsieh、Ralph Müller、Mary L. Bouxsein、Clifford J. Rosen、Margaret E. McCrann、Leah Rae Donahue、Wesley G. Beamer
DOI:10.1359/jbmr.2001.16.2.206
日期:——
To test the hypothesis that factors associated with bone strength (i.e., volumetric bone mineral density [vBMD], geometry, and microstructure) have heritable components, we exploited the 12 BXH recombinant inbred (RI) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high bone mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biomechanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomography (pQCT), and microcomputed tomography (μCT). Segregation patterns of femoral and vertebral biomechanical properties among the BXH RI strains suggested polygenic regulation. Femoral biomechanical properties were strongly associated with femoral width in the anteroposterior (AP) direction and cortical thickness‐geometric properties with complex genetic regulation. Vertebral vBMD and biomechanical properties measured in BXH RI strains showed a greater variability than either B6 or C3H progenitors, suggesting both progenitor strains have independent subsets of genes that yield similar vBMD and strength. The μCT and pQCT data suggested that the distribution of vertebral mineral into cortical and trabecular compartments is regulated genetically. Although the B6 and C3H progenitors had similar vertebral strength, their vertebral structures were markedly different: B6 had good trabecular bone structure and modest cortical bone mineral content (BMC), whereas C3H had high cortical BMC combined with a deficiency in trabecular structure. These structural traits segregated independently in the BXH RI strains. Finally, vertebral strength was not correlated consistently with femoral strength among the BXH RI strains, suggesting genetic regulation of bone strength is site specific.
为了检验与骨骼强度相关的因素(即体积骨矿物质密度[vBMD]、几何形状和微观结构)是否具有可遗传的成分,我们利用了从C57BL/6J(B6;低骨质量)和C3H/HeJ(C3H;高骨质量)亲本品系衍生出的12种BXH重组近交(RI)小鼠品系。对每个BXH RI品系的小鼠股骨和腰椎进行了vBMD、微观结构、生物力学和几何特性的表型特征描述。方法包括弯曲(股骨)和压缩(椎骨)测试、外周定量计算机断层扫描(pQCT)和微型计算机断层扫描(μCT)。股骨和椎骨的生物力学特性在BXH RI品系间的分离模式表明其受多基因调控。股骨的生物力学特性与前后方向(AP)的股骨宽度以及皮质厚度-几何特性强烈相关,这些特性受复杂的遗传调控。BXH RI品系中测量的椎骨vBMD和生物力学特性的变异性比B6或C3H亲本品系更大,表明这两个亲本品系都有独立的一部分基因会产生相似的vBMD和强度。μCT和pQCT数据显示椎骨矿物质在皮质和松质骨隔室中的分布受遗传调控。尽管B6和C3H亲本品系具有相似的椎骨强度,但它们的椎骨结构明显不同:B6具有良好的松质骨结构和适度的皮质骨矿物含量(BMC),而C3H具有高皮质BMC但松质骨结构存在缺陷。这些结构特性在BXH RI品系中独立分离。最后,BXH RI品系中椎骨强度与股骨强度的相关性不一致,表明骨骼强度的遗传调控具有部位特异性。