Animal Models of Joint Injury and Disease

关节损伤和疾病的动物模型

• 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
• 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

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.

类风湿性关节炎 (RA) 和骨关节炎 (OA) 非常普遍，并已达到流行病的程度 在美国和世界范围内，这些关节疾病的特点是炎症、肿胀（尤其是 RA）、 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。 尽管采取了对症止痛措施，但治疗这些疾病的重大缺陷仍然存在，从而支撑了 需要强有力的研究来应对这一紧迫的健康困境。 包括 RA 和 OA 在内的疾病近年来不断发展，有助于加深我们对 疾病病理学、潜在机制、疾病管理和治疗干预。 这些模型的实现的可重复性具有挑战性，特别是在非专家手中，并且由于 跨研究缺乏经过验证的基准标准，同时，对动物行为、敏感性、 和肌肉骨骼功能已被证明在识别啮齿动物的症状和关节功能障碍方面具有价值 然而，关节损伤/疾病模型的创建和功能评估的全谱。 由于可用性有限，大多数研究小组很少使用实现综合分析的结果 核心 D 将通过支持模型实施和功能来满足这一需求。 我们这样做的能力取决于核心领导者的集体专业知识。 炎症性关节疾病（Abu-Amer 博士）、创伤后 OA（O’Keefe 博士和 Shen 博士）和功能性关节病 关节疼痛和功能障碍的评估（Guilak 博士和 Setton 博士）值得注意的是，其中四名研究人员加入了该研究。 WUSTL 研究社区在过去几年中的发展，为我们中心提供了一个独特的机会 开发这个资源核心是我们的目标是推进当前的知识，以弥合我们对知识的理解上的差距。 关节关节炎的细胞、分子和功能基础，并开发和评估新疗法 核心将标准化协议并支持 RA 和 OA 的可重复实施。 我们将促进与核心 B 和 C 的合作，以供研究界广泛使用。 重要的是，核心将组织关键资源，包括设施。 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。 收集和储存来自 RA 和 OA 小鼠模型的组织和血清样本，这些样本将作为 最后，核心将提供所有研究人员进行组织学、基因和蛋白质筛选的标准资源。 实践培训和充实计划，以培训下一代联合调查员。 目标 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。 目的 3：建立小鼠 OA。 目标 4：提供实践培训、推广和丰富。