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Experimental approach may reverse rheumatoid arthritis and osteoporosis
Date:9/21/2009

"While further studies will be required to confirm and detail this mechanism, our results argue strongly that increasing levels of either TRAF3 or NF-κB p100 could represent a powerful new way to limit bone destruction and inflammation-induced bone loss seen in osteoporosis and rheumatoid arthritis," said Brendan Boyce, M.D., professor within the Department of Pathology and Laboratory Medicine at the University of Rochester Medical Center, and the study's corresponding author. "NF-κB p100 levels may vary with each person's genes, making some more susceptible to TNFα-driven disease. Future solutions may be local delivery of p100 into diseased joints via gene therapy, or to target with a drug the enzyme, NIK, which otherwise limits the p100 supply."

At the Center of Bone Loss and Inflammation

Drugs that block the function of TNFα are blockbusters (e.g. Enbrel, Humira and Remicade) because they effectively prevent bone loss and inflammation in most patients with rheumatoid arthritis. They have also been shown to reduce bone loss in women early after menopause.

Other studies, however, have suggested that TNFα cannot cause precursor cells to become osteoclasts unless RANKL first "primes" them. The debate has been spirited because it goes to which molecule should be targeted in near-future attempts to design more precise drugs.

The current results show that TNFα can signal for bone loss without RANKL, providing NF-κB p100 is also absent. By engineering mice with neither RANKL nor NF-κB p100, Boyce and colleagues found that TNFα had greatly increased ability to signal for osteoclast maturation and bone loss in this scenario.

Another unexpected result was measured in changes in gene expression, the process by which information encoded in DNA chains is used to build proteins that make up the body's structures and carry it messages. The team found that mice engineered to over-e
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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