Signalling protein builds bigger, better bones in mice 22/2/05. By the University of Michigan Medical School Genetically engineered mice with bone mass up to four times greater than ordinary mice could lead to new ways of preventing or treating osteoporosis and other human diseases.

Leaping tall buildings in a single bound may be out of the question, but the genetically engineered in Ormond MacDougald's laboratory at the University of Michigan Medical School are definitely stronger than average. The secret appears to be a secreted signalling protein called Wnt10b. Known to inhibit the development of fat tissue in mice, Wnt10b also stimulates the growth of bone cells, according to a study published in the Proceedings of the National Academy of Sciences.

"High levels of Wnt10b expression in bone marrow directly increased bone mass and density in our experimental mice," says Ormond MacDougald (right). "This is the first identification of a specific signaling protein in the Wnt family that regulates bone formation."

Wnt10b is one of a family of 19 related proteins. Wnts (pronounced 'wints') regulate the complex changes that take place as an embryo develops. One step in this process determines the fate of cells that that can become either fat cells called adipocytes or bone-forming cells called osteoblasts. The Wnt10b signal appears to blocks the fat cell pathway and stimulates the osteoblast pathway.

To study the effect of Wnt10b gene expression on tissue development, MacDougald's research team created an artificial sequence of DNA called a transgene linking Wnt10b to the FABP4 promoter, which is expressed in fatty tissue and in bone marrow. The transgene DNA was injected into into fertilised mouse eggs, and then bred mice that inherited the new gene to create the transgenic animals used in their research.

Technology centre: Transgenic mice

The femurs of the transgenic mice had almost four times as much bone, and were mechanically stronger than femurs from control mice. Furthermore, the Wnt10b transgenic mice did not appear to lose their high levels of bone mass with age, and were protected against bone loss due to estrogen deficiency.

Conversely, mice lacking the ability to produce Wnt10b protein in bone marrow cells had 30 percent lower bone volume and bone mineral density than normal mice.

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 signalling in bone marrow and osteoblasts might help prevent the loss of bone associated with ageing or menopause."

Adapted from a news release by University of Michigan Medical School .

Links

Bennett CN, et al. (2005) Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA 22 Feb Epub. Abstract

Ormond MacDougald lab, University of Michigan