For Dr. Jeff Dixon, DDS, PhD, uncovering the intricacies of bone growth is like his own Sherlock Holmes mystery that needs to be solved. For more than two decades, Dr. Dixon, a professor in the Department of Physiology and Pharmacology and Schulich Dentistry, has been investigating how skeletal cells communicate with each other in order to control the formation and destruction of bone.
Two recent grants from the Canadian Institutes of Health Research (CIHR) are enabling Dr. Dixon and his team of outstanding graduate students, postdoctoral fellows and technical staff to look at how physical movement and exercise impact bone growth and the cellular mechanisms that cause this to happen.
When a skeletal cell is stimulated by exercise, it releases ATP and Dr. Dixon and his collaborators have shown that this ATP acts a signal to turn on osteoblasts, the cells that create new bone, and to turn off the osteoclasts, which are the cells that destroy the bone.
This explains why astronauts, like Chris Hadfield, who spend months in weightlessness, lose bone mass. Dr. Dixon’s team proposes that the skeletal cells aren’t being stimulated in the same way they would if they were subjected to physical force like exercise, and therefore ATP isn’t signaling the cells to form new bone.
Using this information, Dr. Dixon and his team are moving on to solving the next mystery and are trying to determine which receptors on the cells are responsible for interacting with the ATP and what goes on inside the cell once this receptor is turned on.
The hope is that it may provide a target for drug interventions to help with conditions like osteoporosis, in which patients experience excessive bone loss.
“If we do pin down which of these receptors are responsible for the beneficial effects of mechanical stimulation on bone, pharmaceutical companies are really interested in this because receptors are a great target for drug interventions,” Dr. Dixon said.
At the moment, there are drugs available to treat osteoporosis, but they generally work by blocking the cells that destroy the bone. The hope is that this research might lead to the development of drugs that will help to rebuild the bone that was lost.
Dr. Dixon is also working in collaboration with Stephen Sims, PhD, from the Department of Physiology and Pharmacology, and Robarts Scientist David Holdsworth, PhD, to build devices to apply mechanical forces to bone cells while they observe them under the microscope. By doing this, they will be able to study the signaling events in living cells as they are being exposed to simulated exercise.
“There are always surprises along the way,” said Dr. Dixon. “We see things in the lab that no one has ever seen before, and that’s a thrill that’s hard to beat.”
This research is supported by CIHR, Canada’s premier agency for health research, and has involved collaborators from Pfizer, one of the world's largest pharmaceutical companies.