Non-pharmacologic interventions for the control of osteoporosis and obesity

Nov 20 2008

The Department of Biomedical Engineering at Stony Brook University received a $1.8 million grant from the National Institutes of Health (NIH) to investigate the biologic and physical mechanisms of very low-magnitude mechanical signals and how they strengthen bone and muscle.

Led by Clinton Rubin, Ph.D., SUNY Distinguished Professor and Chair of Biomedical Engineering, and Stefan Judex, Ph.D., Associate Professor of Biomedical Engineering, the research may provide a foundation to the non-pharmacologic intervention for the control of osteoporosis and obesity.

According to the Centers for Disease Control and Prevention, more than 60 percent of Americans are overweight and obese. In addition, the International Osteoporosis Foundation estimates that approximately 200 million people worldwide suffer from the condition. Regular exercise plays a crucial role in curbing these two diseases, but the Stony Brook University researchers may be on course to developing a new medical means of controlling these diseases.

“We hypothesize that low magnitude mechanical signals drive mesenchymal stem cells (MSCs) toward bone and muscle cell development, thus simultaneously suppressing a path toward cells turning into fat,” says Dr. Rubin. “The manner in which mechanical signals inhibit their pathogenesis remains unknown but may play a significant role in reducing osteoporosis and obesity.”

The collective research of Drs. Rubin and Judex, along with co-investigator Jeffrey Pessin, Ph.D., Director of the Diabetes Research Center at Albert Einstein College of Medicine in New York, leading up to the NIH support showed that high frequency low-magnitude mechanical signals markedly suppress the development of fat cells in laboratory animals by influencing the differentiation pathway of MSCs rather than elevating metabolism. Such results revealed to the researchers a previously unrecognized mechanical means of the regulating fat and bone production.

When Dr. Rubin and colleagues subjected mice to brief daily periods of high frequency (30-90 Hz) and low magnitude (less than 0.4 g) mechanical signals they unexpectedly found that such signals also suppressed the development of fat. Mice exposed to the mild mechanical signals had 29 percent less total visceral abdominal fat compared to mice not exposed to the mechanical signals.

“Our studies are a key step to establishing a non-drug means of inhibiting osteoporosis and obesity,” says Dr. Judex. “We aim to define how the musculoskeletal, adipose and stem cell systems respond to subtle changes in their mechanical environment.”

Dr. Rubin adds that their findings may explain why a sedentary lifestyle is permissive to both osteoporosis and obesity, seemingly distinct diseases, and could suggest how low magnitude mechanical signals reduce the development of fat cells and strengthen the musculoskeletal system as much as defining the fate of MSCs as influencing the resident cell population within bone and fat.

The next steps in the research will be to: 1) Identify genes involved in the tissue response to low magnitude mechanical signals, 2) Evaluate the mechanical symbols influence on dietary and genetic models of obesity, and to 3) Determine if low mechanical symbols influence the differentiation pathway of MSCs.

The mission of the Department of Biomedical Engineering at Stony Brook University is to integrate the cutting edge of engineering and physical sciences with biological sciences to advance the understanding of biomedical problems. Faculty and students use this science to drive the development of therapeutics, diagnostics and medical devices.

http://commcgi.cc.stonybrook.edu/