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Notch controls bone formation and strength
Date:2/24/2008

Notch, a protein known to govern the determination of cell differentiation into different kinds of tissues in embryos, plays a critical role in bone formation and strength later in life, said researchers from Baylor College of Medicine in Houston in a report that appears online today in the journal Nature Medicine. Their findings may provide a basis for understanding osteoporosis and in diseases in which there is too much bone.

We knew that Notch is important in patterning the skeleton, said Dr. Brendan Lee, professor of molecular and human genetics and pediatrics at BCM and a Howard Hughes Medical Institute investigator. After this initial patterning of the skeleton, we saw a dimorphic or two-pronged function for Notch. If there was an increase of Notch activity in bone cells, we get a lot more bone. Notch stimulates early proliferation of osteoblastic cells (cells responsible for bone formation). However, when they knocked out the Notch function in such cells in the laboratory, they found osteoporosis or the loss of bone, similar to age-related osteoporosis in humans.

Mice had an acceptable amount of bone at birth, but as they got older, they lost more and more bone, said Lee, senior author of the report. Loss of Notch signaling might relate to what happens when we get older.

They found that the osteoblasts, which promote bone formation, worked fine when they abolished Notch function in bone forming cells. However, the animals lacked the ability to regulate activity of osteoclasts, whose primary function is to resorb or remove bone. Many women who have osteoporosis actually have a similar problem, an imbalance of bone formation vs. bone resorption. They make enough bone but they resorb bone cells at an abnormally high rate.

In the laboratory, Lee and his colleagues found that when animals were bred to lack Notch, they lost also the ability to suppress bone resorption. That balance between bone formation and resorption allow
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Contact: Glenna Picton
picton@bcm.edu
713-798-4710
Baylor College of Medicine
Source:Eurekalert

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