Breastfeeding must damage bones. A brain hormone may protect them

The study “identifies a new direct loop between the hypothalamus and bone, which is, I think, completely unexpected,” says Sundeep Khosla, a bone researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study.

In the new research, the scientists set out to determine why blocking an estrogen receptor in the hypothalamus resulted in female mice having particularly high bone density. Compared with normal mice, the mutant mice “had a dramatically increased number of bone stem cells,” says stem cell biologist Thomas Ambrosi of the University of California, Davis.

Since the hypothalamus also plays a key role in appetite, the researchers examined diet to see how it would affect bone density and the hormones that are produced. A key piece of the puzzle fell into place when the team found that mutant mice placed on a high-fat diet returned to a normal bone density. An analysis of which bone-strengthening factors were decreased in those mice allowed the team to narrow the list of potential candidates from hundreds to just a handful, says Muriel Babey, an endocrinologist at the University of California, San Francisco.

The scientists then added the substances to mouse stem cells in a petri dish – and found that when treated with CCN3, pieces of bone formed. The team also found that CCN3 levels increased in female mice during lactation, suggesting that CCN3 plays a role in supporting the mother’s bone strength during breastfeeding, when estrogen levels drop.

Next, Ambrosi’s team tested CCN3 in older mice with broken bones, which typically don’t heal well. Applying a patch of hydrogel containing the hormone to injury sites stimulated bone formation, allowing for faster healing. If the hormone works in human skeletal stem cells in a similar way, it could lead to new treatments for osteoporosis (SN: 20.9.18).

Although there are many drugs to prevent bone loss, Khosla says, “we’re still limited in terms of drugs that stimulate bone formation, and especially do it in a sustained way—not just for months, but for years.” .” Because of CCN3’s tissue-building properties, future drugs based on this hormone could potentially increase bone regeneration.

The study “highlights how important the biology and physiology are going on during the reproductive life stages,” says co-author William Krause, a pharmacologist also at UC San Francisco. “There’s potentially a lot of biology out there that remains to be covered.”