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

e bone-making cells.

In both studies, researchers manipulated the osteoblast differentiation process at different stages in study mice. The Long-Hilton study used genetic tools to shut down Notch early in the differentiation process, at the point where the signals would have enabled mesenchymal stem cells to commit to the osteoblast pathway. By interfering early, the Hilton team demonstrated that such signaling normally maintains a pool of mesenchymal stem cells, inhibiting their ability to differentiate into osteoblasts. Thus, shutting down Notch led to an initial increase in osteoblast differentiation and related bone formation. The initial spurt of bone making, however, was followed by decreased production by osteoblasts of osteoprotegerin, a protein that protects the skeleton by inhibiting osteoclast formation. In the absence of Notch, osteoclast formation increased over time, resulting in long-term, age-related bone loss.

While the Hilton team only shut down Notch signaling, the Lee-Boyce study used genetic engineering to greatly increase it in one set of experiments and to shut it down in another. Both sets of changes were made later in the differentiation process than in the Hilton study, near the last step in the pathway where immature osteoblasts mature into active bone-making cells. In the Boyce study, mice genetically engineered to have more Notch signaling in osteoblast precursors had a striking increase in the number of immature osteoblasts, which led to abnormally thickened bones. When they shut down notch signaling, the mice lost bone like those in the Hilton experiments.

After discovering that Notch signaling promotes bone-making cell proliferation, the Lee-Boyce team decided to see if it was involved in bone cancer, given that many cancers results from such uncontrolled growth. The team found that expression of Notch and its signaling partners was significantly higher in samples of primary untreated and post-treatment os
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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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