Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-02-21 DOI:10.1093/jbmrpl/ziae019

Nicole Migotsky, Surabhi Kumar, John T. Shuster, Jennifer C. Coulombe, Bhavya Senwar, Adrian A. Gestos, Charles R Farber, Virginia L Ferguson, Matthew J Silva

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引用次数: 0

Abstract

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that can’t easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of three long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from two populations of genetic diversity. Additionally, we compared how intra-bone relationships varied in the two populations. Our first population of genetic diversity included 72 females and 72 males from the eight Inbred Founder strains used to create the Diversity Outbred (DO) population. These eight strains together span almost 90% of the genetic diversity found in mice (Mus musculus). Our second population of genetic diversity included 25 genetically unique, outbred females and 25 males from the DO population. We show that multi-scale cortical bone traits vary significantly with genetic background; heritability values range from 21% to 99% indicating genetic control of bone traits across length scales. We show for the first time that lacunar shape and number are highly heritable. Comparing the two populations of genetic diversity, we show each DO mouse does not resemble a single Inbred Founder, but instead the outbred mice display hybrid phenotypes with the elimination of extreme values. Additionally, intra-bone relationships (e.g., ultimate force vs. cortical area) were mainly conserved in our two populations. Overall, this work supports future use of these genetically diverse populations to discover novel genes contributing to cortical bone traits, especially at the lacunar length scale.

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两种遗传多样性小鼠模型中雌性和雄性的多尺度皮质骨特征各不相同

了解皮质骨特征的遗传基础可以发现调节骨骼健康的新基因或生物途径。小鼠是骨骼生物学领域应用最广泛的哺乳动物模型，可以量化人类不易评估的特征，如骨细胞裂隙形态。我们的研究目标是调查遗传多样性对骨骼成熟小鼠三块长骨的多尺度皮质骨特征的影响。我们测量了来自两个遗传多样性种群的小鼠骨骼的骨形态、机械性能、材料性能、裂隙形态和矿物质成分。此外，我们还比较了两个种群中骨骼内部关系的变化。我们的第一个遗传多样性群体包括 72 只雌性小鼠和 72 只雄性小鼠，这 72 只雌性小鼠和 72 只雄性小鼠来自 8 个近交创始人品系，用于创建多样性外交群体（DO）。这八个品系几乎涵盖了小鼠（Mus musculus）遗传多样性的 90%。我们的第二个遗传多样性群体包括来自 DO 群体的 25 个遗传独特的外交雌性和 25 个雄性。我们的研究表明，多尺度皮质骨性状随遗传背景的变化而显著不同；遗传率从 21% 到 99% 不等，表明遗传控制了不同长度尺度的骨性状。我们首次发现裂隙形状和数量具有高度遗传性。通过比较遗传多样性的两个群体，我们发现每只DO小鼠都不像单一的近交系创始人，相反，外交系小鼠显示出杂交表型，消除了极端值。此外，骨内关系（如极限力与皮质面积）在我们的两个种群中主要是一致的。总之，这项工作支持未来利用这些基因多样化的种群来发现导致皮质骨特征的新基因，尤其是在裂隙长度尺度上。

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567

期刊介绍： ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric. Indexed/Abstracted： Web of Science SCIE Scopus CAS INSPEC Portico