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A direct path for understanding and treating brittle bones
Date:5/22/2011

Boston - A study by researchers at Children's Hospital Boston and collaborators at other institutions has provided new insights into the means by which bone cells produce new bone in response to mechanical stresses, such as exercise. Their findings lay a path for developing new strategies for treating diseases characterized by low bone density, such as osteoporosis in adults and osteogenesis imperfecta in children.

The research team, led by Matthew Warman, MD, of the Orthopedic Research Laboratories (ORL) in the Department of Orthopedic Surgery at Children's Hospital Boston, published their findings on May 22 in the advanced online edition in Nature Medicine.

Warman, director of the ORL, and his colleagues developed mouse models to better understand the role of a gene called Lrp5 in bone growth. While the gene's exact functions remain unclear, Lrp5 is believed to help mature bone cells called osteocytes respond to changes in mechanical load and call for the production of more bone when needed. Mutations that turn Lrp5 off lead to brittle bones, while others that turn Lrp5 on too much, called high bone mass (HBM) mutations, cause bones to become extra strong.

Using a system that allowed the investigators to selectively express HBM mutations of Lrp5 in osteocytes, the team accurately recreated in the mice the increased bone strength seen in human patients with the same mutations, showing that Lrp5 functions locally in bone to regulate bone mass.

"These HBM mutations seem to fool the osteocytes, the most mature bone cells, into thinking they hadn't made enough bone tissue," said Warman, who is also a Howard Hughes Medical Institute investigator and a professor of genetics at Harvard Medical School. "This knowledge should bolster efforts to develop pharmacologic agents that function similarly to the HBM mutations, in order to trick bone cells into making more bone. In fact, several companies are pursuing these strategies
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Contact: Erin McColgan
erin.mccolgan@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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