More than 200 million people worldwide suffer from osteoporosis, a serious weakening of the bones that increases the risk of fractures. Women are at greater risk of osteoporosis after menopause, because production of the hormone estrogen, which stimulates bone formation, decreases during that period.
Although estrogen levels are also low during breastfeeding, and women also need plenty of calcium to support milk production, osteoporosis and bone fractures are less common during this time. For a long time, the secret to keeping these women’s bones strong has been a mystery. Researchers have long suspected that something other than estrogen is promoting bone growth.
Several years ago, Holly Ingraham, a professor of molecular and cellular pharmacology at the University of California, San Francisco, and her colleagues determined that in female mice—but not in males—blocking a specific estrogen receptor in certain nerve cells led to a significant increase in bone mass. But she couldn’t figure out how at the time.
After years of research, I have now discovered that CCN3 is responsible for this bone building and that this hormone is also present in the same brain region of lactating female mice. Without CCN3 production in these neurons, the lactating female mice rapidly lost bone and their pups began to lose weight, underscoring the importance of the hormone in maintaining bone health during lactation. Based on this discovery, CCN3 has since been named maternal brain hormone (MBH).
stronger bones
When the team applied strategies to increase CCN3 in young and older female or male mice, bone mass and strength increased dramatically over the course of several weeks. In some female mice that had low estrogen levels or were very old, CCN3 could more than double bone mass. When Ingraham’s colleague Thomas Ambrosi, from the University of California, Davis, tested these bones, he was surprised by their strength. He examined the stem cells in the bones, which are responsible for forming new bone, and found that when these cells were exposed to CCN3, they were more likely to produce new bone cells.
To test the hormone’s ability to promote bone healing, the researchers created a hydrogel patch that could be applied directly to the site of a bone fracture and slowly release CCN3 over two weeks. They tested it in older mice whose bone fractures don’t heal properly, and found that the CCN3 patch stimulated new bone formation at the fracture site, which helped the fracture heal.
According to Ambrosi, this is the first time researchers have achieved this kind of mineralization and healing. He now also wants to see if he can use CCN3 in the context of other problems, such as cartilage regrowth, and the hormone’s potential to treat various bone disorders.
Ingraham notes that bone loss occurs not only in postmenopausal women, but also in breast cancer survivors who take certain hormone blockers, in young female athletes, and in older men who have a lower survival rate after hip fracture than older, thin men. She hopes that CCN3 can increase bone mass in all of these scenarios.
