Nov. 19, 2007 Researchers at Cincinnati Children's have issued the first study showing that a protein normally involved in blood clotting (fibrin), also plays an important role in the inflammatory response and development of rheumatoid arthritis. Inflammatory joint disease appears to be driven by the engagement of inflammatory cells with fibrin matrices through a specific integrin receptor, aMB2. Researchers suggest that therapies designed to interrupt the localized interaction of inflammatory cells and fibrin may help arthritis patients.
"Our study establishes that fibrin is a powerful, although context-dependent, determinant of inflammatory joint disease," said Jay Degen, Ph.D., a researcher in Developmental Biology at Cincinnati Children's and the study's lead author. "These findings also suggest that pharmacologically interrupting the interaction of fibrin and aMB2 might be efficacious in the treatment of arthritic disease as well as many other inflammatory diseases, such as multiple sclerosis."
Affecting 2.1 million people in the United States, rheumatoid arthritis is a painful and debilitating disease involving chronic inflammation, tissue degeneration, loss of cartilage and bone and ultimately loss of joint mobility and function, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Although the disease's precise cause is not fully known, activation of specific components in the body's immune system seem to play a major role in its onset and early progression, according to researchers. Fibrin deposits are a prominent feature of arthritic joints and the protein appears to be a link between systems that control inflammation and bleeding within joints. Dr. Degen and his colleagues explained that in arthritic joints, the mesh-like matrices formed by fibrin to create blood clots may control local activity of inflammatory cells as well as support inappropriate tissue reorganization.
The study was conducted by a team that includes researchers from Cincinnati Children's and the University of Cincinnati's College of Medicine using genetically engineered mice with collagen-induced arthritis of the knee and paw. The mice were designed to have selective alterations in the production of fibrinogen, a precursor to fibrin, to allow researchers to evaluate the inflammatory impact of fibrin, especially as it interacts with aMB2.
This research is published in the November issue of The Journal of Clinical Investigation.
The study was supported by a grant from the National Institutes of Health and the Arthritis Foundation. Dr. Degen and the research team are continuing their research to determine more definitively how the interruption of fibrin and aMb2 might translate into potential therapeutic treatment for patients.
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