August 22, 2008

Study Examines How Rheumatoid Arthritis Destroys Bone

FRIDAY, Aug. 22 (HealthDay News) -- New details about how rheumatoid arthritis destroys bone have been uncovered by University of Rochester Medical Center researchers, who said their findings are already helping efforts to create new drugs to reverse the process.

Rheumatoid arthritis, an autoimmune disease that affects about two million Americans, causes swelling, pain and deformity in joints and also thins bone.

Overproduction of the immune system chemical tumor necrosis factor alpha (TNF alpha) leads to the destruction of cartilage and bone in rheumatoid arthritis patients. Along with controlling immune cells, TNF alpha also influences bone mass. It's known that TNF alpha decreases the number of bone-building cells called osteoblasts, but how it does this hasn't been clear.

In experiments with mice, the University of Rochester team found that TNF alpha affects osteoblasts through an enzyme called Smad Ubiquitin Regulatory Factor 1 (Smurf1) which, in turn, turns off two proteins that drive bone-building.

"The significance of our study is that it identifies Smurf1 as the signaling partner through which TNF does its damage in RA-related bone loss," Lianping Xing, assistant professor of pathology and laboratory medicine, said in a university news release.

Xing said the finding "enables us to begin designing small molecule drugs to shut down the action of Smurf1 and its relatives. Furthermore, since mice engineered to have less Smurf1 develop thicker bones, future drugs that shut down Smurf1 may be also useful against more common forms of osteoporosis simply by changing the dose. Of course, this is early stage work with many obstacles ahead, but is exciting nonetheless."

The study was published in the Aug. 22 issue of The Journal of Biological Chemistry.

More information

The Arthritis Foundation has more about rheumatoid arthritis.

-- Robert Preidt
SOURCE: University of Rochester Medical Center, news release, Aug. 22, 2008
id=618616