Protein Implicated in Rheumatoid Arthritis

Researchers have identified a protein involved in the development of rheumatoid arthritis and were able to reduce arthritis in mice by targeting the protein. While far from human application, the finding provides a promising new target for developing therapies for rheumatoid arthritis, a disease that affects over two million people in the U.S.

Rheumatoid arthritis is an inflammatory disease of the synovium, the tissue lining the inside of joints. It brings pain, stiffness, swelling, joint damage and loss of function, most often affecting joints in the hands and feet. It comes about when the immune system, which normally protects the body from infection and disease, mistakenly attacks parts of the body's own joints. Therapies for rheumatoid arthritis traditionally targeted inflammation, with newer treatments focusing on controlling the overactive immune system. Unfortunately, the current treatments aren't completely effective for most people, and suppressing the immune system predisposes people to infections.

Recent research has shown that cells called synoviocytes in the joints of people with rheumatoid arthritis are unusually invasive and aggressive. A research team at Brigham and Women's Hospital led by Dr. Michael B. Brenner hypothesized that the synovium itself might play a role in the development of rheumatoid arthritis. In previous work, they studied a family of proteins called cadherins that help cells to stick together and play an important role in tissue structure and organization. They found that cadherin-11 is involved in the organization of the synovium. To investigate whether cadherin-11 plays a role in rheumatoid arthritis, the research team next turned to mice that spontaneously develop a form of inflammatory arthritis. Their work was funded by NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other organizations.

In the February 16, 2007, issue of Science, the researchers reported that the synovium in mice genetically engineered to lack cadherin-11 had a markedly different organization than in mice with the protein. Strikingly, the severity of arthritis in the mice without cadherin-11 was reduced by half. They also had an 80% reduction in damage to the cartilage in their joints. The researchers then administered a treatment in mice with arthritis to block the activity of cadherin-11 and saw a moderate improvement in their arthritis.

This research shows that cadherin-11 affects the behavior of cells in the synovium and plays a role in inflammatory arthritis. The results from this mouse model, however, may not necessarily be applicable to humans. Whether therapies targeted to cadherin-11 will prove effective against human rheumatoid arthritis is a subject for future research.

— by Harrison Wein, Ph.D.