Animal Models of Joint Injury and Disease

关节损伤和疾病的动物模型

• 批准号: 10388083
• 负责人: YOUSEF ABU-AMER
• 金额: $ 15.07万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 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/10388083
• 关键词: Address; 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; Education and Outreach; Epidemic; Evaluation; Fresh Tissue; Functional disorder; Funding; Gene Proteins; 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; 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; Universities; Washington; arthritic pain; arthropathies; base; biobank; bone; cohort; functional outcomes; interest; joint function; joint injury; mouse model; next generation; novel therapeutic intervention; pain relief; pain sensitivity; programs; repository; treadmill

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.

风湿性关节炎（RA）和骨关节炎（OA）是非常普遍的，并已达到流行病的比例 在美国和世界各地。这些关节疾病的特征在于炎症、肿胀（特别是在RA中）， 疼痛和行动不便尽管在开发抗炎疗法、生物制剂和药物方面取得了重大进展， 症状性疼痛缓解措施，治疗这些疾病的重大缺陷仍然存在，支持 需要强有力的研究来解决这一紧迫的健康困境。广泛的小动物关节模型 疾病，包括类风湿关节炎和OA，近年来已经发展，并有助于促进我们对 疾病病理学、潜在机制、疾病管理和治疗干预。但 这些模型的可重复实施是具有挑战性的，特别是在非专家手中， 缺乏跨研究的有效基准标准。与此同时，动物行为，敏感性， 和肌肉骨骼功能在识别啮齿类动物的症状和关节功能障碍方面具有价值 关节炎模型。然而，关节损伤/疾病模型的创建和功能评估的全方位 由于可用性有限，大多数研究小组很少使用结果来实现全面分析 的基本资源。核心D将通过支持模型的实施和功能来满足这一需求。 评估作为一种综合资源。我们这样做的能力取决于核心领导人的集体专业知识 在炎症性关节疾病（Abu-Amer博士）、创伤后OA（O 'Keefe和Shen博士）和功能性关节炎中， 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 WUSTL研究社区在过去的几年里，这为我们的中心提供了一个独特的机会， 开发这一资源核心。我们的目标是推进当前的知识，以弥合我们理解的差距， 关节炎的细胞、分子和功能基础，并开发和评估新的治疗方法 战略布局核心将标准化协议，并支持RA和OA的可重复实施 供研究界广泛使用的模型。我们将促进与核心B和C的合作， 实现全面分析。重要的是，核心将组织关键资源，包括一个设施， 测试小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 收集和储存RA和OA小鼠模型的组织和血清样品，这些样品将作为 所有研究人员的组织学、基因和蛋白质筛选的标准资源。最后，核心将提供 实际操作培训和充实方案，以培训下一代联合调查员。我们的具体目标 目的1：支持可重复的OA和RA小鼠模型的实施和利用。目标2：提供 生物力学、行为和功能的测量以评估小鼠关节功能。目的3：建立小鼠OA 和RA生物材料库。目标4：提供实践培训、外联和充实。