Scientists discover a dramatic pattern of bone growth in female mice

In the "game-changing" discovery, bone mbad increased by 800% after signals were blocked in the mouse brain.

Scientists at UCLA and UC in San Francisco have discovered a dramatic pattern of bone growth in female mice – research that could potentially lead to greater bone density in women and new treatments for cancer. Osteoporosis in older women.

The researchers found that blocking a particular set of signals from a small number of neurons in the brain causes female but non-male mice to build extremely strong bones and retain them until they reach the end of their life. at an advanced age. These neurons may play an important role in controlling women's bone density, the researchers said. The study was published on January 11 in the journal Nature Communications.

"We believe we have identified a new pathway through which the brain regulates bone density, which is very promising because it allows the body to transform the new bone formation into overdrive," said co-author Stephanie Correa, badistant professor of Integrative biology and physiology at UCLA. and member of the UCLA Brain Research Institute.

More than 200 million people worldwide suffer from osteoporosis, which weakens bones and can easily fracture. Women have a relatively high risk of osteoporosis after menopause.

Correa said the study highlights the importance of studying women, as well as men. "We would have missed that if we only studied men," she said. "The differences between what we see in men and women will give us more clues about the development of these neurons, how they work, and their activity.The more we understand how they work, the more we can manipulate them to improve them. bone health. "

The study began when Correa, then a postdoctoral researcher at UCSF's research laboratory, Holly Ingraham, discovered that genetic suppression of the estrogen receptor protein in neurons in a region of the brain called the hypothalamus had resulted in mild weight loss in altered mice. become less active. Correa was expecting to find that the animals had accumulated extra fat or gained lean muscle, but this was not the case. To find out the source of excess weight, she used more sensitive laboratory techniques that could reveal changes in bone density. To her surprise, she discovered that heavy mice were large. The Ingraham laboratory showed that their bone mbad had increased by 800%.

"I was immediately struck by the magnitude of the effect," Correa said. "We knew immediately that this was changing the game and giving exciting new direction with potential applications to improve women's health."

In addition, the super-dense bones were exceptionally strong.

"Our coworkers who study bones for a living have said they've never seen a bone that strong," said Ingraham, professor of cellular and molecular pharmacology at UCSF. "Our current understanding of how the body controls bone growth can not explain this, suggesting that we may have discovered a completely new pathway that could be used to improve bone strength in older women and men. people with fragile bones. "

Ingraham postdoctoral fellows Candice Herber and William Krause conducted experiments on a specific population of a few hundred estrogen-sensitive brain cells – located in a region of the hypothalamus called the arcuate nucleus – that appeared to be responsible for these dramatic phenomena. increase in bone density. The authors hypothesized that estrogen should normally signal these neurons to displace the energy of bone growth, but that the suppression of estrogen receptors reversed this change.

Additional experiments showed that the modified mice retained their improved bone density until late in life. Normal female mice begin to lose significant bone mbad at the age of 20 weeks, but altered mice retain high bone mbad up to the second year of life, which is considered old for a year. mouse.

Herber and Krause have even been able to reverse the existing bone degeneration in an experimental model of osteoporosis. In female mice that had already lost more than 70% of their bone density due to an experimental decrease in estrogen in the blood, the suppression of the arched estrogen receptors caused bone density to rebound by 50% in a few months. weeks.

Researchers are currently studying how this brain-bone communication occurs and whether drugs could be developed to increase bone strength in postmenopausal women without the potentially dangerous effects of estrogen replacement therapy.

The role of estrogen in the brain is still poorly understood, said Ingraham, whose laboratory studies have shown how estrogen signaling in the brain affects a woman's metabolism at different stages of the life cycle. life.