Chemokine-Based Therapy for Post-Traumatic Osteoarthritis
Abstract
Post-traumatic osteoarthritis is a common form of osteoarthritis that occurs following a physical injury. The injury could be from exercise, a vehicle accident, a fall, a military injury, or any other source of physical trauma. Such injuries can damage the cartilage and/or the bone, changing the mechanics of the joint and making it wear out more quickly. Millions of people around the world suffer from post-traumatic osteoarthritis. It is characterized by inflammation of the joints, caused by progressive cartilage loss, and joint pain that worsens over time. In the United States, about 27 million people live with osteoarthritis. Current treatments such as the use of anti-inflammatory medications like nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control symptoms, but these drugs can cause irritation and ulceration of the lining of the digestive tract, and long-term use may affect blood clotting. Similarly, while steroid injections can help to control inflammation, they can also damage connective tissue and reduce bone density. Thus, there is a pressing need to understand the molecular and cellular mechanisms involved in the development of PTOA in order to develop safer and more effective therapeutic strategies for its treatment. It is known that the expression of molecules involved in inflammation known as cytokines and chemokines, and their receptors, increases during post-traumatic osteoarthritis development. However, their involvement in the progress of the disease is unknown. In this study, we will analyze the role that chemokine interaction with Duffy antigen receptor for chemokines (DARC) plays in post-traumatic osteoarthritis development. Our approach will be (1) to identify the chemokines that interact with DARC to contribute to post-traumatic osteoarthritis development and the time course over which this interaction leads to development of the disease and (2) to determine whether a local blockage of DARC function at the site of an injury will inhibit the inflammatory response and in turn prevent development of post-traumatic osteoarthritis. The results of this project may lead to new strategies effective to prevent the development of post-traumatic osteoarthritis after joint injuries and avoid the side effects of current treatments that sometimes just treat symptoms rather than the disease process itself. Because post-traumatic osteoarthritis is a major health problem in the military that frequently leads to discharge, understanding the molecular and cellular mechanisms involved in the development of the disease will have a significant impact on the well-being of men and women in the Armed Services.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710131
Entities
People
- Bouchra Edderkaoui
Organizations
- Jerry L. Pettis Memorial VA Medical Center
- United States Army