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Chemical messenger controls bone growth in embryos, study finds

St. Louis, April 02, 2002 Scientists at Washington University School of Medicine in St. Louis have for the first time identified a chemical messenger that regulates bone development in the growing embryo. The finding is reported in the April 1 issue of the journal Genes and Development.

This signaling molecule puts the brakes on the cartilage growth that determines the length of bones, says David M. Ornitz, Ph.D., professor of molecular biology and pharmacology, who led the study. First author on the paper was Zhonghao Liu, a graduate student at the School of Medicine.

The messenger, known as fibroblast growth factor 18 (FGF 18), also appears to regulate the hardening, or ossification, of bone. This suggests that FGF 18 coordinates the process by which bones lengthen with the process by which they harden, Ornitz says. That came as a surprise to us.

He believes the study may lead to a better understanding of congenital and genetic diseases that cause bone malformation, and perhaps of cancer and bone diseases such as osteoporosis. Ornitz and his research team engineered mouse embryos that lacked genes for FGF 18. These embryos showed increased growth activity in the bones. For example, in embryos that lacked FGF 18, the growth regions, or growth plates, of the femur were 37 to 60 percent broader than those in normal mouse embryos.

This and other changes seen in the embryos lacking FGF 18 mimic the condition of embryos that lack a receptor molecule known as fibroblast growth factor (FGF) receptor 3. This led Ornitz and his colleagues to conclude that FGF 18 is the messenger molecule for FGF receptor 3.

Receptors are molecules on the surface of cells that trigger some change in the cell when activated by molecules such as hormones or growth factors. Scientists have known for 10 years that FGF receptors are important for skeletal development. For example, mutations in FGF receptor 3 cause achondroplasia, the most common form of dwarfism
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Contact: Darrell E. Ward
wardd@msnotes.wustl.edu
314-286-0122
Washington University School of Medicine
2-Apr-2002


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