Core D-Animal Models of Bone and Joint Injury & Disease

ABSTRACT Rheumatoid arthritis (RA) and osteoarthritis (OA) are highly prevalent conditions that have reached epidemic proportions in the US and worldwide. These joint diseases are characterized by inflammation, swelling, 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, emphasizing the need for additional research to meet this urgent health predicament. Fracture healing is impeded in these and other inflammatory and metabolic diseases, such as aging, obesity, and diabetes, requiring better development of appropriate animal models to study underlying mechanisms and advance therapeutic interventions. A wide range of small animal models of bone and joint disease 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 casual non-experts, and due to scarcity of validated benchmark criteria across studies. At the same time, tests of animal behavior, sensitivity, and musculoskeletal (MSK) function have demonstrated value in identifying symptoms and dysfunction of arthritic joints. Yet, the full spectrum of creation of bone and joint injury/disease models and evaluation of functional outcomes to achieve comprehensive analysis remain scarce due to limited availability of essential expertise or resources. Core D was created to address this need by supporting model implementation and functional assessment as an integrated resource. During its first funding period, Core D implemented eight essential models of murine RA, OA, and bone fracture, established a new, well-equipped pain and functional testing facility, created a murine tissue repository, and carried out a robust training and enrichment program. Our ability to do so rests on the collective expertise of the Core leaders in inflammatory joint disease, post-traumatic OA and bone fracture, and functional assessment of joint pain and dysfunction. Our long-term goal is to advance current knowledge to bridge gaps in our understanding of the basis of bone and joint pathology, and to develop and evaluate new therapeutic strategies. The Core will develop and maintain standard protocols and will (i) support the reproducible execution of RA, OA and bone fracture models for use by the Research Community, (ii) facilitate collaboration with Cores B and C to enable comprehensive analyses, (iii) organize critical resources for testing murine MSK function and behavior, (iv) maintain organized biomaterial resource for tissue and serum samples from RA and OA mouse models, which will be made available to all investigators. Finally, (v) provide hands-on training and enrichment program to train the next generation of joint investigators. Aim 1: Support the implementation and utilization of reproducible OA, RA and fracture 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 and enrichment.