Spotlight on Research 2012

May 2012

Post-Injury Response Could be Key Step in Osteoarthritis Development

Scientists long considered osteoarthritis (OA) a disease of wear and tear. Use the joints long enough, they reasoned, and they are bound to wear out. But research in recent years has suggested that inflammation plays a role in OA, a disease in which joint cartilage breaks down, leaving bone rubbing against bone. A new study, supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, helps confirm that role and points to new targets for treatment, and perhaps prevention, of this common joint disease.

The study, conducted in the laboratory of William Robinson, M.D., Ph.D., at Stanford University, found that a pathway called the complement system, which is a major component of the innate immune system, is critical to the development of OA. Through analyses of joint tissue and joint fluid from individuals with OA, they found that expression and activation of complement is abnormally high in people with OA. The innate immune system is designed to protect the body from harmful invaders such as viruses and bacteria. When cartilage is injured, the researchers found, the complement system is activated, leading to inflammation directed against the body’s own tissues.

While previous research has shown evidence of complement activation in severe, long-standing OA, this study is the first to show the system’s activation may play an important role in the initiation of osteoarthritis and its early progression, says V. Michael Holers, M.D., head of one of the study groups at the University of Colorado.

To confirm that role, scientists used an animal model of OA – mice that develop a disease characteristic of human OA following injury to the stabilizing ligament of the knee joint. When the scientists genetically engineered those mice to lack part of the complement system, however, they did not develop OA. The same results were seen when the mice were treated with an agent developed by Dr. Holers’ lab to inhibit part of the complement system, confirming its role in the development of the disease.

With the insight gained from the study in mice, Dr. Holers says further research is needed to confirm the complement system’s role in the development of OA in humans. If these findings hold true in people, though, blocking a part of the complement system may be an effective treatment for early OA.

Current treatment for OA is primarily limited to relieving symptoms and replacing joints that are too damaged to function well, says Dr. Holers. However, this new research suggests that by giving an agent to block the complement system soon after an injury occurs, doctors may be able to prevent the subsequent occurrence of OA.

Support for this study was also provided by the National Institutes of Health’s National Heart, Lung, and Blood Institute, and the National Institute of Neurological Disorders and Stroke, and other organizations.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.

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Wang Q, et al. Identification of a central role for complement in osteoarthritis. Nat Med. 2011 Nov 6;17(12):1674-9. doi: 10.1038/nm.2543. [PubMed - indexed for MEDLINE] PMID: 22057346