Muscle-Bone Imaging Core

肌肉骨骼成像核心

• 批准号: 10166741
• 负责人: SARAH L DALLAS
• 金额: $ 20.83万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166741
• 关键词: 3-Dimensional; Address; Age; Aging; Animals; Biological Assay; Bone Tissue; Cell Line; Cells; Dendrites; Development; Dinoprostone; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Exercise; Extracellular Matrix; Fiber; Fracture; Goals; Growth; Histologic; Histology; Hypertrophy; Image; Imaging Techniques; Immunohistochemistry; Lead; Measurement; Mediating; Mediator of activation protein; Methodology; Minerals; Mitochondria; Molecular; Monitor; Mus; Muscle; Muscle Cells; Muscle Fibers; Muscle Mitochondria; Muscle Weakness; Muscle function; Musculoskeletal System; Myoblasts; Myosin Heavy Chains; Osteoblasts; Osteocytes; Osteoporosis; Outcome; Pathogenicity; Phenotype; Phosphotransferases; Postdoctoral Fellow; Preparation; Procedures; Protein Biosynthesis; Protocols documentation; Quality of life; Regulation; Reporter; Research; Research Support; Resource Sharing; Role; Running; Sampling; Stains; Standardization; Students; Syndrome; Technical Expertise; Techniques; Tissue Sample; Tissues; Training; Transgenic Mice; Western Blotting; age-related muscle loss; aged; aging population; beta catenin; bone; bone cell; bone imaging; bone loss; bone mass; cell motility; confocal imaging; exercise training; extracellular vesicles; falls; improved; in vivo; indexing; insight; instrumentation; intravital imaging; live cell imaging; mortality; mouse model; multiphoton imaging; muscle form; novel therapeutics; programs; sarcopenia; success; uptake

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.

摘要 肌肉-骨骼成像核心（核心B）将支持本计划项目中所有项目的研究目标。 该计划项目的总体目标是了解肌肉之间的串扰机制 以及可能导致与年龄相关的肌肉和骨骼质量和功能下降的骨骼。另一个目标是 以确定肌肉-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探讨这一全球性问题，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Wnt 3a的作用 和PGE 2/Wnt-β-catenin在骨骼肌衰老中的作用（项目2）;细胞外囊泡在骨-肌肉衰老中的作用 与衰老的相互作用（项目3）;以及雌激素受体介导的骨-肌肉相互作用与衰老的调节 （项目4）。肌肉骨骼成像核心将为所有人提供集中的成像支持和方法 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制备和染色。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 和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。芯会 标准化和整合成像技术，这些技术对肌肉和骨骼表型 在骨细胞或肌肉发生改变的转基因小鼠模型中， 功能，以及已经进行运动训练的小鼠。肌肉骨骼成像核心是至关重要的 所有四个项目的成功和成果。技术专长，仪器，定量分析 核心的标准化协议将提供一个集中的共享资源， 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，并协助描述运动的有益效果 以及这是如何通过肌肉-骨骼串扰来介导的。成功完成 这些项目的研究目标将为骨质疏松症和肌肉减少症同时发生的原因提供新的见解 并且可以鉴定常见致病机制的分子介质和 运动，这可能为新疗法的发展铺平道路。由于肌肉无力导致福尔斯 新的治疗方法解决了这两个方面的“肌肉-骨骼损失综合症”将改善 提高老年人的生活质量和降低死亡率。