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New approach for growing bone comes from Duke preclinical research
Date:10/9/2009

DURHAM, N.C. The natural cycle of building bone to maintain skeletal strength and then breaking it down for the body's calcium needs is delicately balanced, but diseases like osteoporosis break down too much bone without adequate bone replacement, leading to bone fractures.

The results from a new study at Duke suggest a targeted approach by which drugs may be able to fight osteoporosis and other degenerative bone diseases. Diane Gesty-Palmer, M.D., a Duke Assistant Professor of Endocrinology and Metabolism, and her team have found a new mechanism of bone formation in mice that works without inducing the complementary bone breakdown. The work appears in the inaugural issue of Science Translational Medicine.

The science boils down to two biochemical pathways stemming from a cell surface receptor called G-protein coupled receptor (GPCR). This is the largest family of cell surface receptors and the target of numerous drugs for the treatment of many medical disorders. For many years, scientists thought the cellular actions of these receptors were solely controlled by activation of G-protein pathways.

But GPCR discoverer, Duke's Robert J. Lefkowitz, M.D., has also discovered that another molecule, beta-arrestin, works like a brake on G-protein activation. His lab has been learning about ways that beta-arrestin also can signal through different pathways and thus directly control certain cellular processes.

By combining their expertise in bone metabolism and GPCR signaling, Drs. Gesty-Palmer and Lefkowitz have found that beta-arrestin can cause bone to form, even though it blocks receptor activation of the G proteins. They discovered this happens in the receptor for parathyroid hormone (PTH), which regulates the amount of calcium in the body, and is used to treat osteoporosis.

By turning off G-protein signaling with a PTH analogue called PTH-Beta-arr (for beta-arrestin), the researchers were able to separate the
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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