Long typecast as the strong silent type, bones are speaking up.
In addition to providing structural support, the skeleton is a versatile conversationalist. Bones make hormones that chat with other organs and tissues, including the brain, kidneys and pancreas, experiments in mice have shown.
“The bone, which was considered a dead organ, has really become a gland almost,” says Beate Lanske, a bone and mineral researcher at Harvard School of Dental Medicine. “There’s so much going on between bone and brain and all the other organs, it has become one of the most prominent tissues being studied at the moment.”
At least four bone hormones moonlight as couriers, recent studies show, and there could be more. Scientists have only just begun to decipher what this messaging means for health. But cataloging and investigating the hormones should offer a more nuanced understanding of how the body regulates sugar, energy and fat, among other things.
Of the hormones on the list of bones’ messengers — osteocalcin, sclerostin, fibroblast growth factor 23 and lipocalin 2 — the last is the latest to attract attention. Lipocalin 2, which bones unleash to stem bacterial infections, also works in the brain to control appetite, physiologist Stavroula Kousteni of Columbia University Medical Center and colleagues reported in the March 16 Nature.
After mice eat, their bone-forming cells absorb nutrients and release a hormone called lipocalin 2 (LCN2) into the blood. LCN2 travels to the brain, where it gloms on to appetite-regulating nerve cells, which tell the brain to stop eating, a recent study suggests.
Researchers previously thought that fat cells were mostly responsible for making lipocalin 2, or LCN2. But in mice, bones produce up to 10 times as much of the hormone as fat cells do, Kousteni and colleagues showed. And after a meal, mice’s bones pumped out enough LCN2 to boost blood levels three times as high as premeal levels. “It’s a new role for bone as an endocrine organ,” Kousteni says.
Clifford Rosen, a bone endocrinologist at the Center for Molecular Medicine in Scarborough, Maine, is excited by this new bone-brain connection. “It makes sense physiologically that there are bidirectional interactions” between bone and other tissues, Rosen says. “You have to have things to regulate the fuel sources that are necessary for bone formation.”
Bones constantly reinvent themselves through energy-intensive remodeling. Cells known as osteoblasts make new bone; other cells, osteoclasts, destroy old bone. With such turnover, “the skeleton must have some fine-tuning mechanism that allows the whole body to be in sync with what’s happening at the skeletal level,” Rosen says. Osteoblasts and osteoclasts send hormones to do their bidding.
Scientists began homing in on bones’ molecular messengers a decade ago (SN: 8/11/07, p. 83). Geneticist Gerard Karsenty of Columbia University Medical Center found that osteocalcin — made by osteoblasts —helps regulate blood sugar. Osteocalcin circulates through the blood, collecting calcium and other minerals that bones need. When the hormone reaches the pancreas, it signals insulin-making cells to ramp up production, mouse experiments showed. Osteocalcin also signals fat cells to release a hormone that increases the body’s sensitivity to insulin, the body’s blood sugar moderator, Karsenty and colleagues reported in Cell in 2007. If it works the same way in people, Karsenty says, osteocalcin could be developed as a potential diabetes or obesity treatment.