When danger looms, osteocalcin may kick in

Physical things happen in the face of danger. Our heart rate and breathing speed up and we feel something coursing through our body as we debate the decision to fight or flee.

These physiological changes have long been thought to be triggered, at least in part, by the well-known hormone adrenaline – but that may not be the full story.

Researchers led by Columbia University, US, say studies suggest that a lesser-known bone-derived hormone called osteocalcin plays the important role.

As soon as the brain recognises danger it instructs the skeleton to flood the bloodstream with osteocalcin, says senior investigator Gérard Karsenty, and that “completely changes how we think about how acute stress responses occur”.

Karsenty and colleagues have previously shown that when the osteocalcin is released it travels through the bloodstream to affect the functions of the biology of the pancreas, the brain, muscles and other organs. {%recommended 4216%}

A series of studies since then has shown that osteocalcin helps regulate metabolism by increasing the ability of cells to take in glucose, improves memory, and helps animals run faster with greater endurance.

In the new work, described in the journal Cell Metabolism, the researchers presented mice with predator urine and other stressors and looked for changes in the bloodstream. Within two to three minutes, they say, they saw osteocalcin levels spike.

They found similar osteocalcin surges in people when they were subjected to the stress of public speaking or cross-examination.

When osteocalcin levels increased, heart rate, body temperature, and blood glucose levels in the mice also rose as the fight or flight response kicked in.

In contrast, mice that had been genetically engineered so that they were unable to make osteocalcin, or its receptor, were totally indifferent to the stressor. 

“Without osteocalcin, they didn’t react strongly to the perceived danger,” Karsenty says. “In the wild, they’d have a short day.”

As a final test, the researchers were able to bring on an acute stress response in unstressed mice simply by injecting large amounts of osteocalcin.

They say their findings may also explain why animals without adrenal glands and adrenal-insufficient patients – who have no means of producing adrenaline or other adrenal hormones – can develop an acute stress response.

Among mice, this capability disappeared when the mice were unable to produce large amounts of osteocalcin.

“This shows us that circulating levels of osteocalcin are enough to drive the acute stress response,” says Karsenty.