March 15, 2005 | It may not have super hero powers, but scientists studying changes in the skeletal mass of a genetically-engineered “super mouse” agree that it could hold the key to battling debilitating bone diseases.

Larry J. Suva, Ph.D., director of the Center for Orthopaedic Research at the University of Arkansas for Medical Sciences (UAMS) and a member of the UAMS Arkansas Cancer Research Center, was one of several researchers from across the country who collaborated on the study.

Their findings were published Feb. 21 in the online early edition of the “Proceedings of the National Academy of Sciences.”

The “super mice” were genetically-engineered to over-express the protein Wnt10b in their bone marrow. Primitive cells in the marrow, called mesenchymal stem cells, can change either into fat cells or bone-forming cells. Signals from the Wnt10b protein prompted more of the cells to change to bone than fat, creating bigger, denser bones.

Suva and his staff provided detailed skeletal phenotyping of the super mice, comparing them to normal mice and to mice lacking the gene for the Wnt10b protein. Phenotyping means to examine the structure of the body tissue (in this case the skeleton) and identify features considered normal or abnormal. Some structural changes in body tissues can be subtle, but in this case, the changes were radical.

Femur (leg) bones of the super mice had almost four times as much bone as the normal mice, were much stronger and did not show any loss of bone as they aged. The mice lacking the gene for WNT10b protein had 30 percent lower bone volume and density than the normal mice.

“This discovery could help scientists discover how to manipulate the pathway of the WNT10b protein, which in turn could lead to new pharmaceuticals to combat bone diseases like osteoporosis,” said Suva. He said he has already been contacted by other researchers and industries that are extremely interested in the results of the study.

Almost as encouraging as the results of the study was the way it evolved.

Suva said Ormond McDougal, Ph.D., associate professor of molecular and integrative physiology at the University of Michigan Medical School, came to UAMS four years ago for a forum at the Arkansas Cancer Research Center (ACRC). During lunch with a group of researchers from across the UAMS campus, McDougal mentioned his work with the mice and Suva offered his services. The collaboration eventually included several scientists, all who lent their expertise to the discovery.

“This is an example of an interaction that had nothing to do with orthopaedics,” Suva said. He added that the participation by the Center for Orthopaedic Research wasn’t funded by any grant, but was a way for scientists to work together and support each other’s research.

For Suva, that is what the Center for Orthopaedic Research is all about. Whether the subject is aging, cancer, neurology, fitness or a myriad of others, the center can provide information and expertise.

Orthopaedics, and all of UAMS, recently suffered a huge loss with the death of Carl Nelson, chairman and professor of orthopaedic surgery in the UAMS College of Medicine.

“Dr. Nelson had a vision that orthopaedics should be where people came to learn anything they needed to about the musculoskeletal system. He wanted us to be accessible to everybody,” Suva said.

He said that Nelson’s goals for the center continue: to provide the best in education to students, the best in care for patients and the best in research by securing more grants.

The UAMS Department of Orthopaedic Surgery residency program is ranked in the top 50 in the country with medical students from across the country vying for a position annually.  Suva said a big reason for that is the environment of clinical faculty and researchers working together, which is both functional and effective.

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