Transgenic and Mechanical Loading Core

转基因和机械加载核心

• 批准号: 8281060
• 负责人: MARK Louis JOHNSON
• 金额: $ 18.14万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8281060
• 关键词: Age; Aging; Amber; Animals; Applications Grants; Biocompatible Materials; Biomechanics; Breeding; Cell Line; Cells; Data; DsRed; Elements; Engineering; Equipment; Faculty; Felis catus; Female; Forearm; Genotype; Goals; In Vitro; Joints; Knock-out; Knockout Mice; Liquid substance; Mechanics; Methods; Modeling; Molecular; Mus; Muscle; Muscle Cells; Myogenin; Needs Assessment; Osteoblasts; Osteocytes; Osteoporosis; Production; Program Research Project Grants; Property; Regulation; Research; Research Personnel; Resources; Schedule; School Dentistry; Schools; Services; Signal Transduction; Supervision; Testing; Training; Transgenic Mice; Transgenic Organisms; aged; animal colony; animal facility; bone; bone cell; cost effectiveness; dentin matrix protein 1; drug development; experience; fluid flow; in vitro testing; in vivo; male; meetings; mouse model; nanoindentation; operation; oral biology; programs; research study; sarcopenia; sex; stem; success; ulna

instnjctions): The Trangenic and Mechanical Loading Core will support various aspects of all subprojects within the Program Project Grant and is vital to the success of each. The major goal of tills Program Project Grant proposal is to understand the mechanism underiying crosstalk signaling between muscle and bone. A central theme (hypothesis) of all the projects Is that cross talk signaling is a critical component of maintaining the architectural, material and biomechanical properties of bone and the ability of the osteocyte to respond to load. Reciprocally we will detennine If osteocyte derived factors alter the functionality of muscle cells and osteoblasts. The overarching goal of this Program Project Grant is to determine if(how) aging alters these bone properties and/or if aging alters the intrinsic ability of the osteocyte to respond to load and to signal to muscle cells and osteoblasts. The Specific Alms of this Core are: Aim 1: provide mice of the correct sex, genotype and age for the experiments described in Projects 1,2, 3,4. Aim 2: perform in vivo mechanical loading studies for Projects 1 and 4 as needed on the various mouse lines. Aim 3: perform ex vivo mechanical testing to assess the material and biomechanical properties of bones in tiie various lines of mice needed for Projects 1 and 4. Aim 4: perform and support in vitro fiuid flow studies on isolated bone cells and cell lines as a model for testing in vitro the effects of fiuid flow induced loading of these cells In Projects 1,2, 3,4. Cun-ently experiments are proposed using 15 different lines of wildtype, transgenic or knockout mice and this Core will provide the necessary numbers of appropriate genotype, sex and aged mice in support of the studies in the four subprojects. In addition, new transgenic and/or knockout mouse lines will be created or acquired through this core such as the Sost-ERT2-Cre, Sost-tg and Myogenin-Cre mouse lines. Both in vivo and in vitro mechanical loading studies, and all biomaterial and biomechanical assessments needed to guide the studies proposed in the various projects, will be performed using the equipment and resources of this core. This core centralization will provide maximum efficiency and cost-effectiveness in the conduct of the proposed studies. RELEVANCE (See instmctions): This Core will provide centralized support for all subprojects within this Program Project whose goal is to understand the mechanisms underiying crosstalk signaling between muscle and bone and how this is altered by aging. The Core is critical to the success of each of the projects and has the potential to be paradigm changing and result In new targets for drug development for the treamtent of osteoporosis and sarcopenia.

指令）： 转基因和机械加载核心将支持该项目内所有子项目的各个方面 计划项目拨款对于每个项目的成功都至关重要。耕种计划项目补助金的主要目标 提议是为了了解肌肉和骨骼之间串扰信号传导的机制。一个 所有项目的中心主题（假设）是串扰信号是维持 骨骼的结构、材料和生物力学特性以及骨细胞响应的能力 加载。相反，我们将确定骨细胞衍生因子是否改变肌肉细胞的功能和 成骨细胞。该计划项目拨款的总体目标是确定衰老是否（如何）改变这些 骨特性和/或衰老是否改变了骨细胞响应负荷和向骨细胞发出信号的内在能力 肌肉细胞和成骨细胞。该核心的具体施舍是： 目标 1：提供正确性别的小鼠， 项目 1,2,3,4 中描述的实验的基因型和年龄。目标2：进行体内机械 根据需要在不同的小鼠品系上加载项目 1 和 4 的研究。目标 3：离体执行 机械测试以评估不同品系小鼠骨骼的材料和生物力学特性 项目 1 和 4 所需。目标 4：对分离的骨细胞和骨细胞进行并支持体外流体流动研究 细胞系作为模型，用于体外测试流体流动诱导的这些细胞负载的影响在项目 1,2 中， 3,4。目前建议使用 15 种不同品系的野生型、转基因或基因敲除小鼠进行实验 该核心将提供必要数量的适当基因型、性别和年龄的小鼠，以支持 四个子项目的研究。此外，还将创建新的转基因和/或基因敲除小鼠品系 或通过该核心获得，例如Sost-ERT2-Cre、Sost-tg和Myogenin-Cre小鼠系。两者都在 体内和体外机械载荷研究，以及所有生物材料和生物力学评估所需 指导各个项目中提出的研究，将使用以下机构的设备和资源进行 这个核心。这种核心集中化将在实施过程中提供最大的效率和成本效益。 拟议的研究。 相关性（参见说明）： 该核心将为该计划项目内的所有子项目提供集中支持，其目标是 了解肌肉和骨骼之间串扰信号传导的机制以及如何改变它 通过老化。核心对于每个项目的成功至关重要，并且有可能成为范例 改变并导致治疗骨质疏松症和肌肉减少症药物开发的新目标。