Give your skeletal system some credit. Not only do your bones keep you upright, they produce red and white blood cells, store minerals, and help control pH. But that's not all: According to a new study, bones secrete a protein called osteocalcin that regulates sugar and fat absorption. The finding qualifies osteocalcin as a hormone, meaning the skeleton can now add being an endocrine organ to its impressive list of accomplishments.
There have already been hints that the skeletal system and the hormone-releasing endocrine system are intertwined. Gerard Karsenty, a geneticist at Columbia University, showed that fat cells regulate bone mass, for example, by releasing the hormone leptin, which affects the number of bone-building osteoblast cells. Considering the prevalence of feedback systems in the body, he and colleagues wondered whether bones might release their own hormones to influence fat metabolism. They knew that bones secrete a protein called osteocalcin, which helps pack calcium into the skeleton, but because no one had observed this protein acting elsewhere in the body, it was not classified as a hormone. Still, Karsenty and colleagues observed that mice unable to make osteocalcin grow obese, suggesting it might work as a hormone.
So Karsenty's team genetically engineered one set of mice to produce loads of osteocalcin and another set not to make it at all. When fed regular diets, the mice making extra osteocalcin had lower-than-normal blood glucose levels and higher insulin levels than regular mice. Surprisingly, insulin sensitivity increased, too: Normally, a spike in blood insulin lowers the rate at which tissues respond to the hormone--a response that complicates insulin treatment for diabetics. The mutant mice also packed on less fat than regular mice fed high-fat diets. Transgenic mice without osteocalcin developed type 2 diabetes when fed a normal diet, the researchers report in the 10 August issue of Cell. Because osteocalcin is secreted by one organ and acts on others, it fits the definition of a hormone, says Karsenty, making bones part of the endocrine system.
The findings could have important implications for the treatment of diabetes. Osteocalcin has a triple-punch effect, explains Karsenty, in that it raises both insulin levels and insulin uptake while keeping fat at bay. That makes it a promising therapy for middle-aged people who want to fight type 2 diabetes, he says.
The finding offers "the first example of a skeletal factor that has these effects," says endocrinologist Mitch Lazar of the University of Pennsylvania. "It closes the loop" in the fat and bone feedback system, says Bjorn Olsen, a developmental biologist at Harvard Medical School in Boston. "Anyone interested in metabolism control can no longer ignore the skeleton."