"Game-changing" research could lead to novel treatment for osteoporosis in women
Scientists have genetically engineered female mice to develop super strong, dense bones by altering neurons in the rodents' brains. The development could be the first step towards a new treatment for the brittle bone disease osteoporosis in women.
Osteoporosis is a disease that causes bones to lose mass and become structurally weaker, making it more likely that they will fracture. The disease affects over 200 million people worldwide, and is particularly common in women who are past the age of menopause.
A team of scientists working with laboratory mice may have identified a link between bone density and a small number of neurons located in the rodent's brains.
The initial discovery took place when Dr. Stephanie Correa – co-author of the paper detailing the development, and assistant professor of integrative biology and phycology at the University of California at Los Angeles (UCLA) – genetically deleted estrogen receptor proteins in neurons located in the hypothalamus region of the brains of mice. Following the manipulation, the test subjects went on to gain a small but significant amount of weight.
Subsequent observations revealed that the weight gained by the mice was not the result of excess muscle or fat, but instead a massive increase in the rodents' bone density and size. Some of the mice put on up to 800 percent of the bone mass of a non-engineered rodent.
"I was immediately struck by the size of the effect," Dr. Correa said. "We knew right away it was a game-changer and presented a new, exciting direction with potential applications for improving women's health."
Further experiments allowed the team to identify a few hundred estrogen sensitive cells located in a part of the hypothalamus called the arcuate nucleus that were seemingly responsible for governing the bone growth interaction.
The researchers believe that loss of bone mass in older mice could be the result of estrogen signalling the neurons to dedicate less energy to bone growth. By deleting the estrogen receptors, they may have reversed the process.
It was discovered that the genetically engineered mice grew incredibly strong bones, and maintained them well into the second year of their lives. For context, ordinary mice begin to lose bone mass due to old age by their 20th week.
The neuron tampering was also found to reverse bone-loss in mice who had been subjected to a simulated version of osteoporosis. The researchers mimicked the effects of the disease by experimentally lowering the rodents' blood estrogen until they had lost over 70 percent of their bone mass. After the estrogen receptors in the rodent's brains were deleted, the mice were able to regain 50 percent of their bone mass in less than a month.
The technique did not work on any of the male mice involved in the experiments.
"Our collaborators who study bone for a living said they'd never seen bone this strong," said Dr. Holly Ingraham, University of California at San Francisco professor of cellular and molecular pharmacology. "Our current understanding of how the body controls bone growth can't explain this, which suggests we may have uncovered a completely new pathway that could be used to improve bone strength in older women and others with fragile bones."
The team is now researching the method by which the neurons stimulate the bone growth, and experimenting to see whether drugs could be used to increase bone-density in post-menopausal women.
A paper detailing the discovery has been published in the journal Nature Communications.