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Bone quality regulator identified, suggests drug target

UCSF scientists have determined that the quality of bone matrix, a key component of bone, is regulated by a molecule known as transforming growth factor beta. The finding, they say, suggests a possible target for preventing and treating bone fractures associated with aging and genetic diseases.

The study will be reported later this week in the Online Early Edition of Proceedings of the National Academy of Sciences (PNAS).

The ability of bone to resist damage depends on the mass, or quantity, of bone, its architecture and the quality of bone matrix, the mineralized material between cells.

Several molecular factors have been shown to regulate the mass and architecture of bone. So far, however, none have been shown to regulate bone matrix, which is responsible for bone elasticity and toughness.

There has been significant disagreement about whether the quality of bone matrix varies among individuals and, if it does, whether it could be altered for therapeutic reasons. In any case, until now, scientists have lacked a strategy for measuring its quality and teasing out its impact, says senior study author Tamara Alliston, PhD, UCSF assistant adjunct professor of Cell and Tissue Biology.

In the current study, the team explored whether transforming growth factor beta (TGF-) regulates the properties of bone matrix because there were hints that it might. TGF- is known to play a role in the development of osteoblasts, cells that produce bone matrix.

The researchers carried out their evaluation in five sets of mice genetically engineered to produce differing levels of TGF- signaling within osteoblasts, and, for comparison, in normal, or 'wild type' mice. After the animals had been euthanized, the team utilized highly sensitive instruments developed in the materials sciences -- atomic-force microscopy, x-ray tomography and micro-Raman spectroscopy -- to measure the properties of bone matrix independent of bone mass and architectur
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
13-Dec-2005


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