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.

抽象的 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。 该计划项目的总体目标是了解肌肉之间串扰的机制 另一个目标是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。 确定肌肉骨骼串扰是否介导运动对肌肉骨骼的一些有益影响 每个项目都从不同的角度解决这个全球性问题，包括： 肌肉衍生因子 BAIBA 在老年和年轻骨细胞中的作用（项目 1）；骨细胞因子 Wnt3a 的作用； 和 PGE2/Wnt-β-连环蛋白对肌肉衰老的影响（项目 2）；细胞外囊泡在骨肌肉中的作用； 与衰老的串扰（项目 3）；以及雌激素受体介导的骨-肌肉串扰与衰老的调节 （项目 4）。肌肉骨骼成像核心将为所有人提供集中成像支持和方法。 这将包括肌肉和骨骼的共焦和多光子 3D 以及活细胞和活体成像。 以及肌肉组织和矿化组织的组织学制备和染色。 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 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是核心。 标准化和整合对于肌肉和骨骼表型的所有项目至关重要的成像技术 在具有骨细胞或肌肉的转基因小鼠模型中被表征为年龄的函数 功能以及经过运动训练的小鼠至关重要。 所有四个项目的成功和成果。 核心的标准化协议将提供集中的共享资源，从而加速和 加强研究。核心 B 将与动物锻炼和分析核心（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 对肌肉骨骼系统的影响以及这是如何通过肌肉骨骼串扰来介导的。 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 并可以识别常见致病机制和有益作用的分子介质 锻炼，这可能为新疗法的开发铺平道路，因为肌肉无力会导致跌倒。 导致骨折的新疗法将改善这种“肌骨丢失综合症”的两个方面 生活质量并降低老年人口的死亡率。