Animal Models of Joint Injury & Disease

Director

Yousef Abu-Amer
Orthopaedic Surgery
314-362-0335
abuamery@wustl.edu

Associate Directors

Jie Shen
Orthopaedic Surgery
314-747-2567
shen.j@wustl.edu

Farshid Guilak
Orthopaedic Surgery
314-362-8605
guilak@wustl.edu

Regis O'Keefe
Orthopaedic Surgery
314-747-8414
rokeefe@wustl.edu

Mouse Model Database

Debabrata Patra
314-454-8823
patrad@wudosis.wustl.edu

Billing Administrator

Kami McGhee
Orthopaedic Surgery
314-747-5993
314-454-5900 - fax
kjm@wustl.edu

 

 

 

 

 

 

 

Overview

 

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 long-term 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.

 

1. Support the implementation and utilization of reproducible OA and RA mouse models.
Core D will establish and maintain detailed protocols for RA and OA animal models. These protocols will consider various mouse strains, step-by-step technical instructions, consistent sources of reagents to lessen variability, and quality control testing of all materials prior to usage in order to consistently generate the desired joint pathology model. This core will also provide standard analysis guidelines, assist and train users to consistently perform such tests, and direct users to Cores B and C to complete mechanical, imaging and histological analyses.

 

2. Provide measures of biomechanics, behavior, and function to assess mouse joint function.
Using mouse models of RA or OA (Aim 1) or various inbred or genetically modified strains with spontaneous joint changes, mice will be subjected to behavior and function testing by a trained technician under the supervision of Dr. Guilak (Associate Director). The Core will develop and apply protocols to measure mouse locomotion in standing, treadmill running, wheel running, and joint-related pain sensitivities of known value in characterizing arthritis and other musculoskeletal pathologies for evidence of joint-related pain and dysfunction. Through our collaboration with the Washington University Animal Behavior Core (Dr. Wozniak), we will also support generalized measures of behavior and sensorimotor function.

 

3. Establish murine OA and RA biomaterials repository.
Generate cohorts of mice subjected to the range of RA and OA models offered in Aim 1 and, upon completion of functional testing (Aim 2), collect serum and joint tissues of interest for storage in a new bio-bank. Samples will be provided to Cores B and C for comprehensive analyses. These materials and data will be made available as standards for Center researchers.

 

4. Provide hands-on training, outreach and enrichment.
This core will establish educational and training sessions to raise awareness and offer hands on training to interested users to establish RA and OA models. We will organize annual working retreats to bring together RA and OA investigators and promote collaboration. The core will offer Just-In-Time funding to support the conduct of small scale projects to demonstrate feasibility and reinforce the benefits of using comprehensive joint disease assessment with the help of experts in the field.

 


Citing the grant in publications:
“Washington University Musculoskeletal Research Center (NIH P30 AR074992)”