Animal Models of Joint Injury and Disease

关节损伤和疾病的动物模型

基本信息

批准号：
10602567
负责人：
YOUSEF ABU-AMER
金额：
$ 14.9万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10602567
关键词：
Animal Behavior Animal Model Animal Testing Anti-Inflammatory Agents Arthralgia Arthritis Awareness Behavior Benchmarking Biocompatible Materials Biological Assay Biological Products Biology Biomechanics Cells Collaborations Communities Data Degenerative polyarthritis Disease Disease Management Disease model Epidemic Euthanasia Evaluation Fresh Tissue Functional disorder Funding Genes Goals Guidelines Health Histologic Histology Image Immunohistochemistry Inbreeding Inflammation Inflammatory Instruction Joints Knowledge Locomotion Measures Mechanics Medicine Modeling Molecular Mouse Strains Mus Musculoskeletal Pain Pathology Process Proteins Protocols documentation Quality Control Reagent Reproducibility Research Research Personnel Resources Rest Rheumatoid Arthritis Rodent Model Running Sampling Sensorimotor functions Serum Source Standardization Supervision Swelling Symptoms Testing Therapeutic Intervention Time Tissues Training Training and Education Traumatic Arthropathy Universities Washington arthropathies biobank bone cohort functional outcomes interest joint function joint injury mouse model next generation novel therapeutic intervention outreach pain relief pain sensitivity programs repository treadmill

Animal Behavior Animal Model Animal Testing Anti-Inflammatory Agents Arthralgia Arthritis Awareness Behavior Benchmarking Biocompatible Materials Biological Assay Biological Products Biology Biomechanics Cells Collaborations Communities Data Degenerative polyarthritis Disease Disease Management Disease model Epidemic Euthanasia Evaluation Fresh Tissue Functional disorder Funding Genes Goals Guidelines Health Histologic Histology Image Immunohistochemistry Inbreeding Inflammation Inflammatory Instruction Joints Knowledge Locomotion Measures Mechanics Medicine Modeling Molecular Mouse Strains Mus Musculoskeletal Pain Pathology Process Proteins Protocols documentation Quality Control Reagent Reproducibility Research Research Personnel Resources Rest Rheumatoid Arthritis Rodent Model Running Sampling Sensorimotor functions Serum Source Standardization Supervision Swelling Symptoms Testing Therapeutic Intervention Time Tissues Training Training and Education Traumatic Arthropathy Universities Washington arthropathies biobank bone cohort functional outcomes interest joint function joint injury mouse model next generation novel therapeutic intervention outreach pain relief pain sensitivity programs repository treadmill

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项目摘要

Rheumatoid arthritis (RA) and osteoarthritis (OA) are highly prevalent and have reached epidemic proportions in the US and worldwide. These joint diseases are characterized by inflammation, swelling (particularly in RA), pain, and limited mobility. Despite significant advances in developing anti-inflammatory therapies, biologics, and symptomatic pain relief measures, significant shortcomings in treating these diseases remain, buttressing the need for robust research to meet this urgent health predicament. A wide range of small animal models of joint disease, including RA and OA, has been developed in recent years and helped advance our understanding of disease pathology, underlying mechanisms, disease management and therapeutic intervention. However, the reproducible implementation of these models is challenging, especially in the hands of non-experts and due to scarcity of validated benchmark criteria across studies. At the same time, tests of animal behavior, sensitivity, and musculoskeletal function have demonstrated value in identifying symptoms and joint dysfunction in rodent models of arthritis. Yet, the full spectrum of creation of joint injury/disease models and evaluation of functional outcomes to achieve comprehensive analysis is rarely used by most research groups due to limited availability of essential resources. Core D will address this need by supporting model implementation and functional assessment as an integrated resource. Our ability to do so rests on the collective expertise of the Core leaders in inflammatory joint disease (Dr. Abu-Amer), post-traumatic OA (Drs. O’Keefe and Shen) and functional assessment of joint pain and dysfunction (Drs. Guilak and Setton). Notably, four of these investigators joined the WUSTL Research Community in the past few years, which has provided our Center with a unique opportunity to develop this Resource Core. Our goal is to advance current knowledge to bridge gaps in our understanding of the cellular, molecular and functional basis of joint arthritis, and to develop and evaluate new therapeutic strategies. The Core will standardize protocols and support the reproducible implementation of RA and OA models for widespread use by the Research Community. We will facilitate collaboration with Cores B and C to enable comprehensive analyses. Importantly, the Core will organize critical resources, including a facility for testing murine musculoskeletal function and behavior. We will establish a new, organized biomaterial resource to collect and store tissue and serum samples from RA and OA mouse models, which will be made available as a standard resource for histology, gene and protein screens by all investigators. Finally, the Core will provide hands-on training and enrichment program to train the next generation of joint investigators. Our Specific Aims are: Aim 1: Support the implementation and utilization of reproducible OA and RA mouse models. Aim 2: Provide measures of biomechanics, behavior, and function to assess mouse joint function. Aim 3: Establish murine OA and RA biomaterials repository. Aim 4: Provide hands-on training, outreach and enrichment.

类风湿关节炎（RA）和骨关节炎（OA）高度普遍，并且已经达到了流行比例在美国和全球。这些关节疾病的特征是炎症，肿胀（部分在RA中），疼痛和流动性有限。尽管在开发抗炎疗法，生物制剂和有症状的缓解措施，在治疗这些疾病方面存在重大缺点，支撑需要强大的研究来满足这一紧急健康预测。广泛的关节小动物模型近年来已经开发了包括RA和OA在内的疾病，并帮助我们促进了我们对疾病病理学，潜在机制，疾病管理和治疗干预。但是，这些模型的可重复实施具有挑战性，尤其是在非专家的手中在研究中缺乏经过验证的基准标准。同时，对动物行为，灵敏度的测试，肌肉骨骼功能在识别啮齿动物的符号和关节功能障碍方面表现出价值关节炎模型。然而，关节损伤/疾病模型的创建以及功能的评估由于有限的可用性，大多数研究小组很少使用实现全面分析的结果基本资源。核心D将通过支持模型实施和功能来满足这一需求评估作为综合资源。我们这样做的能力取决于核心领导者的集体专业知识在炎症性关节疾病（Abu-Amer博士），创伤后OA（O’Keefe和Shen博士）和功能性关节疼痛和功能障碍的评估（Guilak和Setton博士）。值得注意的是，其中四名调查人员加入了在过去的几年中，Wustl研究社区为我们的中心提供了独特的机会开发此资源核心。我们的目标是促进当前的知识，以弥合我们对关节关节炎的细胞，分子和功能基础，并开发和评估新疗法策略。核心将标准化协议并支持RA和OA的可重复实现研究界宽度使用的模型。我们将促进与核心B和C的合作启用全面分析。重要的是，核心将组织关键资源，包括测试鼠肌肉骨骼功能和行为。我们将建立一个新的，有组织的生物材料资源从RA和OA鼠标模型中收集和存储组织和血清样品，将其提供为所有研究者的组织学，基因和蛋白质筛查的标准资源。最后，核心将提供动手培训和丰富计划，以培训下一代联合调查人员。我们的具体目标是：目标1：支持可再现的OA和RA鼠标模型的实现和利用。目标2：提供评估小鼠关节功能的生物力学，行为和功能的度量。目标3：建立鼠OA 和RA生物材料存储库。目标4：提供动手培训，外展和丰富。