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)和骨性关节炎(OA)非常普遍，并已达到流行的程度 在美国和世界范围内。这些关节疾病的特点是炎症、肿胀(尤其是在RA)、 疼痛，行动不便。尽管在开发抗炎疗法方面取得了重大进展，但生物制剂和 有症状的疼痛缓解措施，在治疗这些疾病方面仍然存在重大缺陷，支撑了 需要强有力的研究来应对这一紧迫的健康困境。各种关节的小动物模型 近年来，包括类风湿性关节炎和骨关节炎在内的疾病得到了发展，并帮助我们加深了对 疾病病理、潜在机制、疾病管理和治疗干预。然而， 这些模型的可重复实施具有挑战性，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，动物行为、敏感度、 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 关节炎的模型。然而，全系列关节损伤/疾病模型的建立和功能评估 由于可获得性有限，大多数研究小组很少使用结果来实现全面分析 必不可少的资源。核心D将通过支持模型实现和功能 将评估作为一种综合资源。我们能否做到这一点取决于核心领导者的集体专业知识 在炎症性关节疾病(阿布-阿梅尔博士)、创伤后骨性关节炎(奥基夫和沈博士)和功能性 评估关节疼痛和功能障碍(Guilak和Setton博士)。值得注意的是，其中四名调查人员加入了 在过去的几年里，WUSTL研究社区为我们的中心提供了一个独特的机会 开发此资源核心。我们的目标是推进当前的知识，以弥合我们对 关节关节炎的细胞、分子和功能基础，以及开发和评估新的治疗方法 战略。核心将使协议标准化，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，以 启用全面分析。重要的是，核心组织将组织关键资源，包括 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本，这些样本将作为 所有研究人员筛选组织学、基因和蛋白质的标准资源。最后，核心将提供 实践培训和充实计划，以培训下一代联合调查员。我们的具体目标 目标1：支持可复制的骨性关节炎和类风湿关节炎小鼠模型的实施和利用。目标2：提供 测量生物力学、行为和功能以评估小鼠的关节功能。目的3：建立小鼠骨性关节炎模型 和RA生物材料库。目标4：提供实践培训、外联和充实。