Muscle-Bone Imaging Core

摘要 肌肉-骨骼成像核心(核心B)将支持该计划项目内所有项目的研究目标。 该项目的总体目标是了解肌肉之间串音的潜在机制。 和骨骼，这可能是与年龄相关的肌肉、骨量和功能下降的原因之一。另一个目标是 确定肌肉-骨骼串扰是否介导了运动对肌肉骨骼的一些有益影响 系统。每个项目都从不同的角度处理这一全球问题，包括： 老年和年轻骨细胞中的肌源性因子BAIBA(项目1)；骨细胞因子WNT3a的作用 和PGE_2/WNT-β-连环蛋白在肌肉衰老中的作用(项目2)；细胞外小泡在骨骼-肌肉中的作用 与衰老的串扰(项目3)；以及雌激素受体介导的骨骼-肌肉与衰老的串扰调节 (项目4)。肌肉骨骼成像核心将为所有人提供集中成像支持和方法 项目。这将包括共焦和多光子3D和活细胞以及肌肉和骨骼的活体成像 以及肌肉组织和矿化组织的组织学准备和染色。它还将支持 定量组织形态计量学和动态骨组织形态计量学、免疫组织化学、肌纤维分型 以及3D骨细胞共聚焦成像以及线粒体动力学和功能的实时成像。核心将会 标准化和集成所有肌肉和骨骼表型项目所必需的成像技术 在骨细胞或肌肉改变的转基因小鼠模型中被表征为年龄的函数 功能，以及接受过运动训练的小鼠。肌肉-骨骼成像核心至关重要 为所有四个项目的成功和成果干杯。技术专长、仪器设备、定量分析 和核心的标准化协议将提供集中的共享资源，这将加速和 加强研究。核心B将与动物运动和分析核心(核心C)协调其活动。 支持所有项目的研究目标，并协助确定锻炼的有益效果 关于肌肉骨骼系统以及肌肉-骨骼串扰是如何调节这一点的。成功完成 这些项目的研究目的将为骨质疏松症和骨质疏松症同时发生提供新的见解。 并可确定常见致病机制的分子介体及其有益效果 运动，这可能为新疗法的开发铺平道路。因为肌肉无力会导致摔倒 导致骨折，针对这两个方面的“肌肉-骨丢失综合征”的新疗法将得到改善 提高老年人口的生活质量，降低死亡率。

ABSTRACT The Muscle-Bone Imaging Core (Core B) will support the research aims of all projects within this program project. The overall aim of the program project is to understand the mechanisms underlying crosstalk between muscle and bone that may contribute to the age related decline in muscle and bone mass and function. Another goal is to determine if muscle-bone crosstalk mediates some of the beneficial effects of exercise on the musculoskeletal system. This global question is addressed by each project from a different perspective, including: the effects of the muscle-derived factor, BAIBA, in old and young osteocytes (Project 1); the effects of osteocyte factors Wnt3a and PGE2/Wnt-β-catenin on muscle with aging (project 2); the role of extracellular vesicles in bone-muscle crosstalk with aging (Project 3); and estrogen receptor-mediated regulation of bone-muscle crosstalk with aging (Project 4). The Muscle-Bone Imaging Core will provide centralized imaging support and methodologies for all projects. This will include confocal and multiphoton 3D and live cell and intravital imaging of muscle and bone as well as histological preparation and staining of muscle tissues and mineralized tissues. It will also support quantitative histomorphometry and dynamic bone histomorphometry, immunohistochemistry, muscle fiber typing and 3D osteocyte confocal imaging as well as live imaging of mitochondrial dynamics and function. The core will standardize and integrate imaging techniques essential for all the projects in which muscle and bone phenotypes are being characterized as a function of age in transgenic mouse models with altered osteocyte or muscle function, as well as mice that have been subjected to exercise training. The Muscle-Bone Imaging Core is critical to the success and outcomes in all four projects. The technical expertise, instrumentation, quantitative analysis and standardized protocols of the Core will provide a centralized shared resource that will accelerate and enhance the research. Core B will coordinate its activities with the Animal Exercise and Analysis Core (Core C) to support the research aims of all the projects and to assist with characterizing the beneficial effects of exercise on the musculoskeletal system and how this is mediated by muscle-bone crosstalk. Successful completion of the research aims of these projects will provide new insight into why osteoporosis and sarcopenia occur together and may identify molecular mediators of common pathogenic mechanisms and of the beneficial effects of exercise, which may pave the way for development of new therapies. As muscle weakness contributes to falls that lead to fractures, new therapies addressing both aspects of this “muscle-bone loss syndrome” will improve quality of life and reduce mortality in the aged population.