Resource Based Center for Musculoskeletal Biology and Medicine (Overall Application)

摘要/摘要-总体 在美国，每两个成年人中就有一个患有普遍的肌肉骨骼疾病，相关费用为900美元 每年10亿美元。为了应对这场危机，有效利用资源和持续致力于基本 翻译研究是必不可少的。我们建议华盛顿大学基于资源的中心 肌肉骨骼生物学和医学，致力于两个长期目标-推进对 肌肉骨骼疾病的生物学基础，并开发和测试基于生物的干预措施 战略。我们代表着一个由81名研究人员组成的动态研究社区，隶属于17名学者 各部门。自2009年以来，该中心发表了343篇论文，被引用6687次。 中心调查人员每年的外部资金为6620万美元，其中包括来自NIAMS的810万美元。我们的 工作重点是最普遍和最昂贵的肌肉骨骼疾病-关节炎、背痛、骨骼和 关节创伤、骨质疏松症和转移性癌症。值得注意的是，我们的大部分研究工作都在 基础研究和临床前研究。因此，我们的总体目标是支持研究界在 肌肉骨骼生物学和医学动物模型的开发、实施和评价。 我们将通过四个综合目标来实现这一目标。目标1.通过行政核心(A)， 提供中心领导以管理核心并参与外展。指导一项浓缩计划 这将通过试点促进下一代肌肉骨骼研究人员的发展 可行性计划、研讨会、座谈会等活动。目的2.通过肌肉骨骼结构 和力量核心(B)，支持获取、培训和成本效益高的利用：i)基于X射线的成像 方法量化的形态，以及ii)生物力学方法量化的力学性能 肌肉骨骼组织(骨、肌腱、肌肉、软骨、椎间盘)。目标3.通过肌肉骨骼 组织学和形态测量核心(C)，进行组织处理、包埋、切片和染色， 适用于所需组织/技术范围的方案维护和用户培训 肌肉骨骼研究。支持获得和培训常规和高级显微镜和 组织形态计量学。目的4.在关节损伤和疾病核心(D)的动物模型上，提供训练和 可复制的骨关节炎和类风湿性关节炎小鼠模型的实现。活体测量 生物力学和行为，以评估关节疼痛和功能。创建组织和血清的存储库 来自关节炎小鼠模型的样本。总而言之，我们提议的四个核心将提供必要的支持 为我们的研究社区开发、实施和评估肌肉骨骼动物模型 生物和医学。每个核心的一个共同主题是支持培训和充实活动，以 促进下一代肌肉骨骼研究人员的发展。

Summary/Abstract - Overall One in two adults in the United States has a prevalent musculoskeletal condition, with related costs of $900 billion annually. To address this crisis, efficient utilization of resources and sustained commitment to basic and translational research are essential. We propose the Washington University Resource-Based Center for Musculoskeletal Biology and Medicine, dedicated to two long-term goals – to advance research on the biological basis of musculoskeletal disease, and to develop and test biologically based intervention strategies. We represent a dynamic Research Community of 81 investigators, affiliated with 17 academic departments. Since 2009, the Center has contributed to 343 publications that have been cited 6687 times. The annual external funding of Center investigators is $66.2 million, including $8.1 million from NIAMS. Our work focuses on the most prevalent and costly musculoskeletal disorders – arthritis, back pain, bone and joint trauma, osteoporosis, and metastatic cancer. Notably, the majority of our research endeavors are in basic and pre-clinical studies. Therefore, our overall objective is to support the Research Community in the development, implementation and evaluation of animal models for musculoskeletal biology and medicine. We will address this objective through four integrated Aims. Aim 1. Through an Administrative Core (A), provide Center leadership to manage the Cores and engage in outreach. Direct an Enrichment Program that will foster the development of the next generation of musculoskeletal investigators through a Pilot & Feasibilty program, seminars, symposia and other activities. Aim 2. Through the Musculoskeletal Structure and Strength Core (B), support access, training and cost-effective utilization for: i) x-ray based imaging methods to quantify morphology, and ii) biomechanical methods to quantify mechanical properties of musculoskeletal tissues (bone, tendon, muscle, cartilage, disc). Aim 3. Through the Musculoskeletal Histology and Morphometry Core (C), perform tissue processing, embedding, sectioning and staining, protocol maintenance and user training appropriate for the range of tissues/techniques required in musculoskeletal research. Support access and training for routine and advanced microscopy and histomorphometry. Aim 4. In the Animal Models of Joint Injury and Disease Core (D), provide training and implementation for reproducible mouse models of osteoarthritis and rheumatoid arthritis. Measure in vivo biomechanics and behavior to assess joint pain and function. Create a repository of tissue and serum samples from arthritic mouse models. In summary, the four Cores we propose will provide essential support for our Research Community to develop, implement and evaluate animal models for musculoskeletal biology and medicine. A common theme for each Core is to support training and enrichment activities to foster development of the next generation of musculoskeletal investigators.