Muscle and Bone Maintenance in Hindlimb Suspended Rats

后肢悬吊大鼠的肌肉和骨骼维护

• 批准号: 6469071
• 负责人: CHARLOTTE A. PETERSON
• 金额: $ 35.29万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6469071
• 关键词: apoptosis; atrophy; bone density; bone disuse atrophy; cell differentiation; cell proliferation; densitometry; exercise; gravity; homeostasis; immobilization of body part; laboratory rat; limbs; microarray technology; muscle cells; muscle function; muscle proteins; muscle satellite cell; musculoskeletal disorder therapy; protein biosynthesis

DESCRIPTION (provided by applicant): The goal of this proposal is to perform a comprehensive analysis of a novel form of resistance exercise training as a countermeasure to offset the loss in musculoskeletal structure and function after exposure to microgravity. Rats, continuously maintained in a hindlimb suspended state, will be subjected to resistance training using flywheel technology. We hypothesize that this form of resistance training, that is gravity-independent, will prevent muscle atrophy and loss of bone mineral density normally associated with hindlimb suspension. Force generated during training will be quantitated using a load cell and correlated with skeletal muscle mass, fiber cross-sectional area, and performance in Aim I. To identify specific mechanisms responsible for the changes in muscle properties in response to flywheel training, the dynamics of muscle protein homeostasis will be systematically quantitated. Aim 2 will explore the effects of flywheel training on bone mass, density and strength. Quantitation of the strain required for maintenance of bone properties using a strain gage will be correlated to muscle force to allow the development of a training regimen that is beneficial to the entire musculoskeletal system. The relative contribution of apoptotic muscle fiber nuclear loss and osteocyte apoptosis to loss of musculoskeletal function during hindlimb suspension and the effect of flywheel training will be determined in Aim 3. Finally, in Aim 4, muscle and bone marrow stem cells will be isolated and proliferation and differentiation analyzed to determine if changes in these cellular processes potentially contribute to the response to hindlimb suspension and flywheel resistance training. This approach will provide a basic understanding of mechanisms contributing to maintenance of the musculoskeletal system via resistance exercise during microgravity. Our experiments are directly relevant to studies being carried out in humans to determine efficacy of flywheel training protocols. Together, results may provide insight into the use of resistance exercise as a countermeasure to the loss of muscle and bone that occurs during space flight.

描述（由申请人提供）：该提案的目的是执行 对新型抵抗运动训练形式的全面分析 抵消肌肉骨骼结构和功能损失的对策 暴露于微重力后。老鼠不断维持在后肢 悬浮状态，将使用飞轮进行抵抗训练 技术。我们假设这种抵抗训练形式，即 不依赖重力，将防止肌肉萎缩和骨矿物质的丧失 密度通常与后肢悬挂有关。产生的力 训练将使用负载电池进行定量，并与骨骼相关 肌肉质量，纤维横截面区域和AIM I的性能 负责肌肉特性变化的特定机制 对飞轮训练的反应，肌肉蛋白稳态的动力学将 系统地定量。 AIM 2将探索飞轮的影响 训练骨骼质量，密度和力量。定量 使用应变量表维持骨骼性能所需的是 与肌肉力量相关，以开发训练方案 对整个肌肉骨骼系统有益。相对贡献 凋亡的肌肉纤维核损失和骨细胞凋亡 后肢悬架期间的肌肉骨骼功能和飞轮的影响 训练将在AIM 3中确定。最后，在AIM 4中，肌肉和骨髓 干细胞将被分离出来，并分化为增殖和分化 确定这些细胞过程中的变化是否有可能有助于 对后肢悬架和飞轮抵抗训练的反应。这种方法 将提供对有助于维持的机制的基本理解 微重力期间通过抵抗运动的肌肉骨骼系统。我们的 实验与在人类中进行的研究直接相关 确定飞轮训练协议的功效。结果可能会 提供有关使用抵抗运动作为对策的见解 在太空飞行期间发生的肌肉和骨骼的丧失。