Effects of Genetics, Exercise, and Age on Bone Mechanics

描述（由申请人提供）：本项目将采用两种新方法研究遗传背景、运动和衰老对骨骼性能的相关作用。首先，已知遗传背景的老鼠被挑选出来进行高水平的自愿运动，它们将在有或没有跑步轮的情况下长大。这将允许遗传和运动对骨骼功能的影响在统计上相互分离。其次，将使用综合骨分析方法，从微观材料特性到大体骨形态，研究整个股骨近端。纳米压痕和微型计算机断层扫描将允许对小鼠股骨进行高度精确的有限元分析。该项目的其他目标包括确定运动时的矿化和重塑模式，确定运动时股骨的高应力区域，以及评估骨折力学模型。除了在这个项目中解决骨生物学的基本问题，结果将允许更好地理解遗传，运动和衰老之间的关系，这将对骨质疏松症的预测和诊断具有重要意义。

DESCRIPTION (provided by applicant): This project will examine the relative roles of genetic background, exercise, and aging on bone performance, using two new approaches. First, mice, which are of known genetic background and which have been selected for high levels of voluntary exercise, will be raised with and without access to a running wheel. This will allow genetic and exercise effects on skeletal function to be statistically separated from one another. Second, a comprehensive bone analysis approach will be used, in which the entire proximal femur will be studied, from microscale material properties to gross bone morphology. Nanoindentation and micro-computed tomography will allow highly accurate finite element analysis of the mouse femora. Additional aims of this project include the determination of mineralization and remodeling patterns in response to exercise, the identification of areas of high stress in the femur during locomotion, and evaluation of models of fracture mechanics. In addition to the fundamental questions of bone biology addressed in this project, the results will permit a better understanding of the relationship between genetics, exercise, and aging, which will have significant implications for the prediction and diagnosis of osteoporosis.