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Finding Key Master Switch for Bone Development Reported

Finding Key Master Switch for Bone Development Reported
M. D. Anderson News Release 01/10/02

Scientists at The University of Texas M. D. Anderson Cancer Center have identified a novel transcription factor required for bone formation.

A research team led by Dr. Benoit de Crombrugghe, chairman of the Department of Molecular Genetics at M. D. Anderson, report the discovery in the January 11 issue of the journal Cell.

"The importance of our research right now is that it provides proof of a key master switch that regulates gene expression in bone development," Dr. de Crombrugghe said, "but we believe it has future potential for human health problems, including cancer." 

He noted that finding the new factor responsible for bone formation has eventual applications to studies aimed at preventing osteoporosis, a disease that affects millions of people around the world, especially post-menopausal women.  His group's research also should help in designing a diagnostic tool for classifying bone tumors and in accelerating efforts to keep breast, prostate and other cancers from spreading to patients' bones.

The journal article outlines laboratory and animal research conducted during the past three years at M. D. Anderson to understand the basic mechanisms that regulate gene expression in bone development. 

"Despite the fact that cells in all issues and organs have the same genes, we know that each cell type turns on and off different sets of genes.  Many scientists are trying to identify the so-called 'master transcription factors' that turn on these different sets of genes in different cell types. Only a small number of such master switches have been identified previously. One of those is Runx2, which is needed for development of cells known as osteoblasts," Dr. de Crombrugghe explained.

Two young researchers in his laboratory, Dr. Kazuhisa Nakashima and Ms. Xin Zhou, hypothesized that another master switch was necessary for the development of osteoblasts, which are needed for bone formation. Working with other members of Dr. de Crombrugghe's group, they discovered a second transcription factor and named it Osterix. (A patent application has been submitted on the discovery and its potential uses.)

The researchers were able to prove their theory by generating "knockout" mice in which the Osterix gene was removed. The mice without the gene had normal cartilage but did not develop bones, according to Dr. de Crombrugghe, who holds the Paul and Mary Haas Chair in Genetics at M. D. Anderson. 

In addition to Dr. Nakashima, a research associate, and Ms. Zhou, a research investigator, other authors for the journal article include Dr. Richard Behringer, a professor of molecular genetics; research laboratory coordinators Zhaoping Zhang and Jian Min Deng; and Dr. Gary Kunkel, who during the early research was a visiting professor from Texas A&M University, where he is in the Department of Biochemistry and Biophysics.

01/10/02


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