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Same process discovered to both form skeleton and protect it for life
Date:3/12/2008

A protein signaling pathway recently discovered to guide the formation of the skeleton in the fetus also keeps bones strong through adult life, according to two papers published recently in the journal Nature Medicine. Furthermore, the same mechanism may be at the heart of osteoporosis, where too little bone is made over time, and bone cancer, where uncontrolled bone growth contributes to tumors. Lastly, the results argue that an experimental Alzheimers drug may also be useful against bone cancer.

Human cells must be able to send signals that switch life processes on and off as they form the fetus, and later, to maintain the integrity of adult tissue. Notch proteins have been recognized for many years as part of signaling cascades that drive the development of the fetal brain, nerves and blood vessels. What had remained a mystery was whether Notch has any role in bone formation and health in adults.

The current results demonstrate for the first time in live, adult animals that genetic changes made to increase Notch signaling specifically in bone-making cells (osteoblasts) resulted in thickened, abnormal bone similar in some ways to that seen in osteosarcomas, a type of bone cancer. Conversely, eliminating notch resulted over the long term in the weaker bones seen in osteoporosis. The studies confirm that Notch plays a role in bone development, and suggest it also maintains bone strength with aging. The data also provide the first evidence that Notch, connected in the past with leukemia and intestinal tumors, may also play a role in the development of osteosarcoma.

The findings are important because without Notch signaling in osteoblasts, the cells that build bone, you get inadequate new bone formation along with aggressive bone destruction by bone-degrading cells, both typical of osteoporosis, said Brendan Boyce, M.D. professor of Pathology at the University of Rochester Medical Center, and a study author. In addition, normal Notch
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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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