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NIH grant will fund IUPUI research into collagen's role in bone fracture resistance

Indiana University

A biomedical engineer researcher at Indiana University-Purdue University Indianapolis has received a $419,000 National Institutes of Health grant to uncover why mechanical loading of bones increases their resistance to fractures.

Discovery of the biological mechanism behind that would advance research on whether physical properties of collagen in bones can be manipulated to increase fracture resistance in patients suffering from diseases related to bone fragility, said Joseph Wallace, assistant professor of Biomedical Engineering in the Purdue School of Engineering and Technology.

"We think, based on evidence in the lab, that mechanical loading is beneficial, but no one really knows how or why," Wallace said. "The question this research is designed to answer is what is happening to drive that on a biological, molecular and cellular level?"

Most people think bones as a static thing in the body, he said. "Nothing could be further from the truth. Bone is one of the most metabolically active tissues in the body. It changes its size and shape according to the type of loading it encounters."

When people walk or run, for example, they put a load, or force, on their bones that impacts them. Mechanical loading is a load placed on a bone by a machine.

Over the last 10 years, researchers have turned their attention to collagen, a protein that exists in bone and other tissues in the body such as muscle, tendons and ligaments, Wallace said. Collagen in bones acts like steel bars in reinforced concrete, enabling bones to more bendable without cracking.

"It's now recognized that collagen may be as or more important than the mineral component of bone," Wallace said. "Actually it is probably the interaction between collagen and the mineral that is most important."

Under the grant, Wallace will collaborate with IU School of Medicine bone researchers as he seeks to explain the biological mechanism.

"Our hypothesis is that mechanical loading alters the expression and activity of collagen-modifying proteins and assembly/packing machinery that are affected in many matrix-related bone diseases," he said. "The ultimate goal is to deliver a new understanding of mechanically-induced adaptation in bone and to provide new ways to target bone disease through mechanical alterations to collagen."

The research is expected to show that mechanical modulation of collagen is a practical method to prevent or treat disease-induced changes in bone quality and fracture resistance, Wallace said. It will challenge the current mineral/mass/architecture-centered dogma for controlling fracture, which neglects the contribution of collagen, Wallace added.


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