How Nerve Cells Work in Fractures…

Newswise — Sticks and stones may break one’s bones, but healing them requires the production of a protein signal that stimulates the generation, growth and spread of vital nerve cells, or neurons, throughout the injured area. That’s the finding of a recent Johns Hopkins Medicine study that used mice to demonstrate what likely takes place during human fracture repair as well.

“A better understanding of how nerve cells work in bones could spur the development of neuron regenerating therapies for people with diseases where nerve damage is common, such as diabetic neuropathy,” says Aaron W. James, M.D., Ph.D., associate professor of pathology at the Johns Hopkins University School of Medicine and co-senior author of the study described in the Journal of Clinical Investigation.

“Typically, people with these conditions also have problems with bone repair," he adds.

Essentially, the scientists say their results in mice demonstrate that, at the fracture point, two proteins — one called tropomyosin receptor kinase-A, or TrkA, and the other known as nerve growth factor, or NGF — bind together to signal the start of innervation, the supplying of nerves, and subsequently, new bone. They say that this process may be similar to the mechanism for human bone repair.

“We showed that when TrkA, and in turn, NGF, were removed from the process, there was a dramatic reduction not only in innervation but also in the three follow-up activities critical to successful recovery from a fracture: blood vessel formation, production of bone-synthesizing cells and mineralization of new bone,” says James. “In fact, the drop overall in these indicators of bone repair was between 60% and 80%.”

First identified in the 1950s, NGF is now known to direct the growth, maintenance, proliferation and preservation of neurons throughout the body. It also helps neurons alert the brain when tissues, including bones, are experiencing pain from injury or disease. Studying this connection, James says, is what led researchers to suspect that NGF also might play a key role in skeletal repair.

“When drug companies in recent years developed and conducted human trials of anti-NGF agents to reduce pain from arthritis and other disorders, they found that a number of patients suffered unusual bone fractures,” says Johns Hopkins researcher and co-senior author Thomas Clemens, Ph.D. “Other studies around the same time showed that the bones of children with a rare genetic mutation preventing the production of TrkA may not heal well after injury, suggesting a connection between this signaling pathway and bone repair mechanisms.”

 

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