Establishing biomechanical mechanisms in mouse models: practical guidelines for systematically evaluating phenotypic changes in the diaphyses of long bones.
Establishing biomechanical mechanisms in mouse models: practical guidelines for systematically evaluating phenotypic changes in the diaphyses of long bones.
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DOI：
10.1002/jbmr.2539
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
van der Meulen MC
中科院分区：
文献类型：
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作者：
Jepsen KJ;Silva MJ;Vashishth D;Guo XE;van der Meulen MC
小鼠广泛用于骨骼生物学研究，通过机械测试评估小鼠的骨骼是评估实验扰动的功能影响时的关键步骤。例如，基因敲除可能针对骨形成中重要的途径，并导致“低骨量”表型。但骨骼承受功能负荷的能力如何？例如，骨骼在负载过程中变形的程度以及骨骼的抗骨折能力如何？通过对骨形态、密度和机械特性的系统评估，研究人员可以建立“生物力学机制”，通过实验扰动改变整个骨骼的机械功能。本综述的目的是阐明这些生物力学机制，并为系统评估小鼠骨骼的表型变化提出建议，重点关注长骨骨干和皮质骨。此外，建议测试条件和结果变量的最低可报告标准，这将改善研究之间数据的比较。回顾了基本的生物力学原理，然后描述了横截面形态特性，这些特性最能说明给定实验扰动的净细胞效应，并且与生物力学功能最相关。尽管形态很关键，但全骨的机械性能只能通过机械测试来准确确定。回顾了刚度、最大载荷、屈服后位移和断裂功的功能重要性。由于骨骼和身体尺寸通常密切相关，因此根据体重调整全骨特性的策略是详细的。最后，使用真实数据提出了一个综合框架，并回顾了文献中的几个例子，以说明如何综合小鼠长骨的形态、组织水平和全骨力学特性。
Mice are widely used in studies of skeletal biology, and assessment of their bones by mechanical testing is a critical step when evaluating the functional effects of an experimental perturbation. For example, a gene knockout may target a pathway important in bone formation and result in a “low bone mass” phenotype. But how well does the skeleton bear functional loads; eg, how much do bones deform during loading and how resistant are bones to fracture? By systematic evaluation of bone morphological, densitometric, and mechanical properties, investigators can establish the “biomechanical mechanisms” whereby an experimental perturbation alters whole-bone mechanical function. The goal of this review is to clarify these biomechanical mechanisms and to make recommendations for systematically evaluating phenotypic changes in mouse bones, with a focus on long-bone diaphyses and cortical bone. Further, minimum reportable standards for testing conditions and outcome variables are suggested that will improve the comparison of data across studies. Basic biomechanical principles are reviewed, followed by a description of the cross-sectional morphological properties that best inform the net cellular effects of a given experimental perturbation and are most relevant to biomechanical function. Although morphology is critical, whole-bone mechanical properties can only be determined accurately by a mechanical test. The functional importance of stiffness, maximum load, postyield displacement, and work-to-fracture are reviewed. Because bone and body size are often strongly related, strategies to adjust whole-bone properties for body mass are detailed. Finally, a comprehensive framework is presented using real data, and several examples from the literature are reviewed to illustrate how to synthesize morphological, tissue-level, and whole-bone mechanical properties of mouse long bones.