Scientists discover new hormone that strengthens bones

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Researchers at UC San Francisco (UCSF) and UC Davis have made an exciting discovery about a hormone that keeps the bones of breastfeeding women strong.

This hormone, called CCN3 or “maternal brain hormone,” could also help heal bone fractures and treat osteoporosis in the general population.

Their findings were published in the journal Nature.

Holly Ingraham, Ph.D., a professor at UCSF, led the study. She emphasized the importance of studying female mice, as this discovery might have been missed if only male mice were used.

“This shows how crucial it is to study both male and female animals to fully understand biology,” she said.

Osteoporosis is a severe weakening of the bones that affects over 200 million people worldwide, leading to frequent fractures. Women are especially at risk after menopause due to lower levels of estrogen, a hormone that helps build bones.

Interestingly, breastfeeding women also have low estrogen levels but rarely suffer from osteoporosis, suggesting another factor helps maintain bone strength.

In previous research, Ingraham’s lab found that blocking a specific estrogen receptor in certain neurons in female mice resulted in significantly stronger bones. They suspected a hormone in the blood was responsible but couldn’t identify it until now.

In the new study, the researchers discovered that CCN3 is the hormone responsible for increased bone strength in mutant female mice. They found CCN3 in the brains of lactating female mice and confirmed its importance in maintaining bone health during breastfeeding. Without CCN3, the female mice lost bone mass, and their babies began to lose weight.

The researchers tested the hormone in young and old mice, both male and female, and found that increasing CCN3 levels significantly boosted bone mass and strength. In some female mice without estrogen or very old mice, CCN3 more than doubled their bone mass.

Thomas Ambrosi, Ph.D., a collaborator from UC Davis, tested the strength of these bones and found them to be much stronger than usual. He also discovered that CCN3 stimulated stem cells within the bones to generate new bone cells.

To test CCN3’s ability to heal fractures, the team created a hydrogel patch that released the hormone over two weeks. In elderly mice, this patch helped fractures heal more effectively, promoting the formation of new bone.

“We’ve never seen this level of bone healing with any other method,” Ambrosi said. The researchers are excited to explore other potential uses for CCN3, such as regrowing cartilage.

The team plans to study CCN3’s molecular mechanisms and its impact on bone health in various conditions. Ingraham highlighted the potential benefits of CCN3 for post-menopausal women, breast cancer survivors, elite female athletes, and older men.

“It would be incredibly exciting if CCN3 could increase bone mass in all these scenarios,” she said.

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