Fight of Flight May Be in Our Bones

Fight of Flight May Be in Our Bones

Have you ever felt your heart beating out of your chest when you're about to present in front of a large group, or take a high stakes exam? This intense physiological response to high stress levels is often referred to as “Fight or Flight” where the sympathetic division of the autonomic nervous system kicks into overdrive, resulting in an increase in heart rate, temperature, respiration, and blood glucose levels. While this norepinephrine (noradrenalin) based response originally evolved in our ancestors to protect us from predation and other potentially life threatening situations, this same mechanism is still triggered in modern humans by seemingly innocuous circumstances. 

A recent controversial study conducted by physician and geneticist Gerald Karsenty at the Columbia University Irving Medical Center supports the claim that at least part of our fight-or-flight response is mediated by the release of a hormone from our bones called osteocalcin. When Karsenty first started his work on osteocalcin over 20 years ago, he originally set out to investigate the role of osteocalcin in the calcification and hardening of bone. However, when Karsenty and his team knocked out the gene encoding for osteocalcin in mice, he noticed that the calcification process remained undisturbed, and that the rodents lacking the protein began to accumulate excess body fat, and have trouble breeding. These results were surprising, and led Karsenty and his team to propose that osteocalcin was a hormone, released into the blood by the skeleton, to help regulate functions in other parts of the body. 

Karsenty and his colleagues began to wonder why the skeleton (involved in protection and movement) also has the ability to act as an endocrine organ. This led researchers to the unusual hypothesis that perhaps bones may have evolved, in part, to help animals escape from danger. If this hypothesis is correct, then it would make sense for the bones to somehow contribute to the fight-or-flight response. The team believed that osteocalcin was able to activate the sympathetic branch of the autonomic (involuntary) nervous system, and performed a second experiment where osteocalcin was injected directly into the bloodstream of mice. However, the protein appeared to have no activity on the sympathetic nervous system and instead led to a rapid decrease in activity in the parasympathetic (rest and digest) branch of the ANS. This suggested that osteocalcin works by inhibiting parasympathetic branch of the ANS, in turn allowing for the fight-or-flight reaction controlled by the sympathetic branch to occur.

In contrast to this, Dr. Elefteriou (a former postdoctoral researcher in Karsenty’s lab) notes that Karsenty has his critics. In fact, many members of the bone research community have been unable to replicate these results, and have posted studies reporting the absence of endocrine abnormalities in mice lacking osteocalcin. Dr. Elefteriou commented on the research stating that “There are people who are in awe in front of this data and think it’s exciting...and some people who, because it’s so controversial, don't believe a thing”.  

Overall, no conclusions regarding the role of osteocalcin in the fight-or-flight response can be made without conducting further research. However, the data exhibited in Karsenty’s study does  inspire the scientific community as a whole to re-evaluate our overly simplistic view of stress, and the fight-or-flight response. So next time you experience that heart pounding, palm sweating stress, consider the fact that it is part of human nature, and may or may not be “in your bones”. 

Posted by Kayla Rosiello (3)