According to a study published in an edition of the Journal of Biological Chemistry, researchers have been able to find out the key details of how rheumatoid arthritis (RA) could possibly destroy bone.

The findings are seen as already guiding efforts to design new drugs for reversing loss of bone related to rheumatoid arthritis and may even address more common forms of osteoporosis (bone loss) with a few adjustments.

From Sciencedaily.com:

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. While the new drugs are effective for many patients, others experience infections and even lymphoma in a few cases. The new drugs are based on bioengineered versions of proteins made by human immune cells called antibodies, and are very expensive to make. Thus, the field has been searching for smaller, simpler chemicals that would be effective, but with lower costs and fewer side effects.

“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 Lianping Xing, Ph.D., 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.”

This study provided the first direct proof that the TNF alpha affects osteoblasts through an enzyme that in turn shuts down two otherwise bone-building proteins, through Smad Ubiquitin Regulatory Factor 1 (Smurf1).