Researchers have discovered key details of how rheumatoid arthritis (RA) destroys bone, according to a study published in the Aug. 22 edition of the Journal of Biological Chemistry. The findings are already guiding attempts to design new drugs to reverse RA-related bone loss and may also address more common forms of osteoporosis with a few adjustments.
Two million Americans suffer from rheumatoid arthritis (RA), which causes swelling, pain and deformity in joints and also lead to the thinning of bone. In autoimmune diseases like RA, the body's disease-fighting immune cells mistakenly identify parts of a person's body as foreign invaders, akin to bacteria, and produce chemicals to destroy them. Among the immune chemicals known to play a central in autoimmune disease is tumor necrosis factor alpha (TNF alpha), which ramps up the production of immune cells and chemicals as part of the body's response to disease. When overproduced in RA patients, TNF alpha signals for the destruction of cartilage and bone.
Beyond its control over immune cells, TNF alpha also influences bone mass. Human bone is continually regenerated to maintain strength. Under the control of signaling molecules which include TNF alpha, two cell types, balanced against each other, make bone recycling possible. Osteoclasts break down aging bone to make way for new bone, while osteoblasts build new bone at the sites where osteoclasts have removed it. Going into the study, the field understood that TNF alpha decreases the number of bone-building osteoblasts, but not how. The current study provides the first direct proof that the TNF alpha affects osteoblasts through an enzyme called Smad Ubiquitin Regulatory Factor 1 (Smurf1), which in turn shuts down two proteins that would otherwise drive bone-building.
http://www.sciencedaily.com/releases/2008/08/080820163233.htm