DEVELOPMENT AND REMODELING OF BONE USING EXPERIMENTAL LOADING

使用实验负载进行骨骼的发育和重塑

• 批准号: 3877578
• 负责人: KENNETH GORDON
• 金额: --
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3877578
• 关键词: bone density; bone development; bone fracture; electron microscopy; femur; gravity; infant animal; laboratory mouse; mature animal; physiologic bone resorption; skeletal stress

The broad objectives of this project are to examine and differentiate key structure parameters of the mouse femur that change during conditions of differential loading and are responsible for a change in the ultimate breaking strength of the femur. Preliminary results indicate that developing mouse femora when exposed to two types of increased functional loading for 30 days responded by increasing the ultimate breaking strength by up to 74% by changing predictable structural features. However, the structural feature, that were changed to achieve this increased breaking strength were not the same for each experimental treatment. The specific aims of this study are to 1) Correlate the specific structural and mineral density changes with the stimulus that elicited the response. 2) Correlate the structural and mineral density changes with the related increase in breaking strength. 3) Determine if the structural changes seen in mice exposed to differential functional and experimental loading are consistent and long lasting among age groups, from developing to adult mice. Two working hypotheses are proposed: 1) chronic bending moments of moderate intensity elicit structural changes in the femur that mainly increase cortical cross-sectional area and rotational moment of inertia, and 2) short duration high intensity bending moments elicit changes in trabecular architecture and rotational moment of inertia but no changes in cortical cross- sectional area. Mice will be divided into three functional treatment groups: normal exercise control (NE) short duration hypergravity (4G), and chronic burrowing (high litter cage) (HL). Treatments will last for 30 days and will be initiated on day 14, 60 or 518 of age. Experiments will run from 44 to 548 days. A second experimental phase will use pure bending moments of known magnitudes delivered by a stress machine. Applied stresses will be of two types: short duration high intensity, and longer duration low intensity. Undecalcified femora will be sectioned and examined under the scanning electron microscope for cross- sectional area and rotational moment of inertia. Serial cross sections of undecalcified femora will be used to reconstruct the three dimensional architecture of trabecular bone. Cortical and trabecular bone d:ta will be quantified with the aid of a visual analysis system. Mounted sectioned and ground undecalcified femora will be used for X-ray micro-analysis determinations of calcium and phosphorus densities. Prepared femora will be tested for ultimate breaking strength with an Instron Materials Tester. Results of this study may have application to the development of structurally sound bones in children and the remodeling of bone in the osteoporotic elderly.

该项目的主要目标是检查和 区分小鼠股骨的关键结构参数 在不同负载条件下的变化是 导致最终断裂强度的变化 股骨。 初步结果表明，发育中的小鼠股骨 当暴露于两种类型的增加功能负荷 30 小时时 天通过增加极限断裂强度来回应 通过改变可预测的结构特征，提高到 74%。 然而， 结构特征，被改变以实现这种增加 每个实验的断裂强度并不相同 治疗。 本研究的具体目标是 1) 将 特定结构和矿物质密度随刺激而变化 这引起了回应。 2）关联结构和 矿物密度随着破碎率的增加而变化 力量。 3) 确定小鼠体内是否出现结构变化 暴露于不同的功能和实验负载是 从发育中到各个年龄组之间的一致性和持久性 成年小鼠。 提出了两个工作假设：1）慢性 中等强度的弯矩引起结构变化 主要增加皮质横截面积的股骨和 转动惯量，以及 2) 持续时间短、强度高 弯曲力矩引起小梁结构的变化和 转动惯量但皮质交叉点没有变化 截面积。 小鼠将被分为三种功能 治疗组：正常运动控制（NE）短期 超重力（4G）和慢性挖洞（高窝笼）（HL）。 治疗将持续 30 天，并于第 14 天开始， 60岁或518岁。 实验将持续 44 至 548 天。 一个 第二个实验阶段将使用已知的纯弯矩 由压力机提供的幅度。 施加的应力将 有两种类型：短持续时间高强度和较长持续时间 持续时间低强度。 未脱钙的股骨将被切片 并在扫描电子显微镜下检查交叉 截面积和转动惯量。 串行交叉 未脱钙的股骨部分将用于重建 骨小梁的三维结构。 皮质和 骨小梁 d:ta 将借助视觉进行量化 分析系统。 安装切片和磨削的未脱钙股骨 将用于钙的 X 射线微量分析测定 和磷密度。 准备好的股骨将进行测试 使用英斯特朗材料测试仪测定极限断裂强度。 这项研究的结果可能会应用于开发 儿童骨骼结构健全以及骨骼重塑 骨质疏松的老年人。