Scientists have discovered a novel hormone that strengthens bones

Scientists have discovered a novel hormone that could prove to be a breakthrough in the treatment of osteoporosis, a devastating disease that causes brittle bones.

More than 200 million people worldwide suffer from osteoporosis, a disease that weakens bones and causes regular fractures. Women are particularly vulnerable after menopause because of lower levels of estrogen, which helps build bone. Interestingly, despite low estrogen levels during breastfeeding, the bones of breastfeeding women remain forceful even as they lose calcium into their milk, suggesting that another factor may promote bone growth.

Scientists at UCSF and UC Davis who have been investigating this mystery have discovered in a study of mice that a maternal brain hormone (CCN3) increases bone density and strength in female mice. The results test were published in the journal Nature.

Scientists had previously found that blocking a specific estrogen receptor in some brain neurons led to significant increases in bone mass in female mice. Suspecting a blood hormone was responsible, the researchers searched and identified CCN3 as a key factor.

Although CCN3 didn’t seem like a typical hormone secreted by neurons, its presence in the brains of nursing female mice confirmed its role. The researchers noted that without CCN3, the nursing mice lost bone and their babies lost weight. Scientists now call CCN3 maternal brain hormone (MBH).

“One of the remarkable things about these findings is that if we hadn’t studied female mice, which is unfortunately the norm in biomedical research, we might have missed this finding entirely. It underscores how significant it is to look at both male and female animals throughout their lives to fully understand the biology,” said Holly Ingraham, senior author of the study, in Press Release.

When researchers increased CCN3 levels in juvenile adult and older mice, their bone mass and strength increased significantly within weeks. In some female mice without estrogen or very senior ones, CCN3 increased bone mass by more than two-fold.

“There are situations where highly mineralized bones are not better; they may be weaker and actually break more easily. But when we tested these bones, they were much stronger than normal,” said Thomas Ambrosi, a research associate on the study.

The researchers also observed that bone stem cells were more likely to generate novel bone cells when exposed to CCN3. To test whether CCN3 could lend a hand bone heal, the researchers designed a hydrogel patch that would slowly release CCN3 at the site of a bone fracture. Fractures are typically hard to heal in older mice, but the CCN3 patch promoted novel bone growth at the fracture site, leading to a more youthful healing process.

“We’ve never been able to achieve this level of mineralization and healing with any other strategy. We’re really excited to continue this and potentially apply CCN3 to other issues, like cartilage regrowth,” Ambrosi said.