A recent discovery of a hormone, called Maternal Brain Hormone (CCN3), shows significant potential for bone medicine. This hormone, which helps maintain bone strength in lactating women, could also have applications in the treatment of fractures and osteoporosis in the general population.
Researchers at the University of California, San Francisco (UCSF) and the University of California, Davis have shown that CCN3 increases bone density and strength in mice.
Published on July 10 in the journal Nature, These findings address a long-standing mystery about the ability of women’s bones to stay strong during breastfeeding, despite the elimination of calcium for milk production.
Holly Ingraham, PhD, lead author of the study, stressed the importance of studying both male and female animals to gain a complete understanding of biology.
Osteoporosis affects more than 200 million people worldwide and It is a particularly serious problem for postmenopausal women, due to the decrease in estrogen, hormone crucial for bone formation. Interestingly, during lactation, estrogen levels are also low, but the incidence of osteoporosis and fractures is lower, suggesting the presence of other factors that promote bone health.
Ingraham’s lab had previously identified that blocking a specific estrogen receptor in female mice led to a significant increase in bone mass, suggesting the existence of a responsible hormone, the search for which lasted for years. Finally, CCN3 was identified as the key factor in the mutant females, since CCN3 did not fit the typical profile of a hormone secreted by neurons.
CCN3 in a specific region of the brain of suckling mice was decisive
The lack of this hormone resulted in rapid bone loss in lactating female mice and weight loss in their offspring, highlighting its importance for bone health during lactation. Based on this discovery, researchers began referring to CCN3 as Maternal Brain Hormone (MBH).
The effectiveness of CCN3 is not limited to lactating female mice. Strategies to increase circulating levels of this hormone in young and old mice, both male and female, showed dramatic increases in bone mass and strength.
In female mice without estrogen or very old, CCN3 managed to double bone mass. Thomas Ambrosi, PhD, assistant professor of orthopaedic surgery at UC Davis, observed that bones treated with CCN3 were noticeably stronger than normal bones.
Analysis of stem cells responsible for generating new bone tissue revealed that CCN3 increased the propensity of these cells to form new bone. To assess CCN3’s ability to heal fractures, the researchers developed a hydrogel patch that slowly released the hormone at the site of a fracture. In aged mice, this patch stimulated the formation of new bone, speeding up healing.
Ambrosi highlighted the exceptional mineralization and healing achieved with CCN3, an achievement unprecedented with other strategies. The researchers plan to explore the molecular mechanisms of CCN3, its levels in lactating women, and its potential to treat various bone conditions. Muriel Babey, MD, co-senior author and physician-scientist in the UCSF Division of Endocrinology, is excited to investigate how CCN3 affects bone metabolism in clinically relevant disease situations.
In partnership with the UCSF Catalyst program, William Krause, PhD, will begin to translate these results into clinical applications. Ingraham noted that Bone loss affects not only postmenopausal women, but also breast cancer survivorselite athletes and older men, highlighting the broad therapeutic potential of CCN3.
Keep reading:
- Narcissism decreases with age: study
- Alzheimer’s: Nasal spray eliminates tau proteins in mouse brains
- Popular weight loss drugs linked to lower cancer risk