By Dana Yamashita
Humans have just over 200 bones in their bodies. Chances are, during the course of your life, you will have either broken one of them or know someone who has — bone fractures are among the most common injuries in the United States. In fact, according to the Guinness Book of World Records, famed stunt performer Evel Knievel suffered 433 bone fractures.
Our bones are not only part of our skeletal system, they also work with our ligaments, tendons, and joints to provide movement; protect our internal organs; house bone marrow, the main source of blood formation in humans; and serve as a source of calcium for the entire body.
Recent research by an international team of scientists and engineers led by Deepak Vashishth, director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute, has found that a loss of enzymatic processes within the body can increase a person’s risk of bone fracture.
Enzymatic processes are essential to any number of chemical reactions occurring within the body, including the production of the extracellular matrix within bone that is critical for mechanical support. Phosphorylation — one of those key enzymatic processes — is the attachment of a phosphoryl to a protein, and is crucial for cellular regulation. This process plays a role in many diseases, but until now, researchers didn’t know if it altered tissue integrity and organ function.
The researchers looked at osteopontin, a protein that plays a vital role in holding the matrix together. They developed a process by which they could induce phosphorylation — or its counterpart, dephosphorylation — in bones from genetically modified mice, some that had osteopontin and others that did not.
The team found that the measure of a bone’s mechanical strength increased with osteopontin phosphorylation and declined with dephosphorylation.
“This is the first study that lays down that phosphorylation in bone matters, particularly how it assists bone in releasing energy, and that loss of this modification is bad for bone,” Vashishth said.
Additionally, the team studied the effect of osteopontin phosphorylation levels in two rare bone diseases that are associated with skeletal deformities. In both cases, osteopontin phosphorylation levels decreased, a finding that lays the groundwork for further exploration. The team’s findings may also be applied to similar processes within other connective tissues and possible therapeutics to counteract abnormal osteopontin phosphorylation levels.
“Osteopontin is not only in bone, it’s in other tissues in our body, like our kidneys and several other places,” said Vashishth. “This research can also shed light on other things that can happen throughout the body.”
Vashishth and his lab worked with researchers at McGill University in Canada, the University of Southampton in the United Kingdom, the University of Patras in Greece, Aarhus University in Denmark, and Vienna University of Technology in Austria. The research was supported by a grant from the National Institutes of Health’s National Institute of Arthritis and Musculoskeletal and Skin Diseases.