Using PCR analysis of Wnt10b-expressing cells in bone marrow, MacDougald found high levels of collagen and alkaline phosphatase, and expression of transcription factors that turn on genes involved in bone formation.
Bennett discovered another important clue when she found that Wnt10b expression shuts down activity of a gene called PPAR-gamma, which is required for the development of adipocytes or fat cells. "It suggests that Wnt10b's role may be to block PPAR-gamma, shifting development from the adipocyte pathway to the osteoblast pathway," she says.
In future research, MacDougald hopes to unravel the molecular mechanism for Wnt10b's bone-building effect. "It's not only an important scientific question, it's important to the understanding and potential treatment of osteoporosis and other human diseases," he says. "Right now, there is a need for drugs on the market to stimulate new bone formation. Being able to activate Wnt signaling in bone marrow and osteoblasts might help prevent the loss of bone associated with aging or menopause."
The research was funded by the National Institutes of Health, the U-M Diabetes Research and Training Center, the U-M Core Center for Musculoskeletal Disorders, and the Nathan Shock Mutant and Transgenic Rodent Core. Fellowships to Christina Bennett were from the Tissue Engineering and Regeneration Training Grant and the American Physiological Society Porter Fellowship. Kenneth Longo was supported by a mentor-based postdoctoral fellowship from the American Diabetes Association.
The experimental mice used in the study were produced in the U-M's Transgenic Animal Model Core facility. The University of Michigan has filed for patent protection on the Wnt10b transgenic mouse.
Additional collaborators on the study include Kenneth A.
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21-Feb-2005