A study published in the Aug. 22nd issue of the Journal of Biological Chemistry reports that researchers have found key ways rheumatoid arthritis (RA) destroys bones.
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,” according to a University of Rochester Medical Center press release.
As we all know, an autoimmune disease like RA functions by mistaking parts of our bodies as foreign invaders (like a bacteria) — and then producing chemicals to destroy them. Paramount among them is the immune chemical tumor necrosis factor alpha (TNF alpha).
Additionally, TNF alpha influences bone mass. Here’s how:
“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.”
How does this knowledge help us?
According to the study, it shows us our focus on “biologic” medications is a good start: “While traditional RA drugs like NSAIDs and steroids treat symptoms, a newer class of best-selling drugs (e.g. Humira, Remicade and Enbrel) reverses the disease process by shutting down TNF alpha activity,” the press release says.
The treatments are not perfect yet. While effective for many patients, some experience infections or lymphoma (though, as CreakyJoints has reported before, autoimmune disease patients already carry a higher risk for lymphoma just by the nature of their illness).
Researchers are also trying to lower costs.
“The new drugs are based on bioengineered versions of proteins made by human immune cells called antibodies, and are very expensive to make,” the press release says. “Thus, the field has been searching for smaller, simpler chemicals that would be effective, but with lower costs and fewer side effects.”
Which is a much better position to be in, compared to just ten years ago.
“The significance of our study is that it identifies SMURF1 as the signaling partner through which TNF does damage in RA-related bone loss,” said Dr. Lianping Xing, assistant professor of Pathology and Laboratory Medicine at the University of Rochester Medical Center. “That has enabled researchers to begin designing small molecule drugs to shut down the action of Smurf 1 and its relatives.
“Furthermore, since mice engineered to have less Smurf1 expression 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 it is exciting nonetheless.”
To read the University of Rochester Medical Center’s press release (and more details on the study’s history), click on the link below:
Researchers discover how rheumatoid arthritis causes bone loss, site accessed on 08/25/08