A hormone produced in the gut appears to limit bone formation, scientists report in Cell [subscription required]. The hormone, serotonin, is the same one produced by the brain to regulate mood, learning, and sleep, but the new study finds that serotonin produced by the gut has an entirely separate function. Mice engineered to produce extra serotonin formed weak bones, while mice engineered to produce less serotonin developed extra-strong bones. The research, though still basic, suggests new avenues of osteoporosis research in humans. “It’s what you’d call a landmark study,” Bjorn Olsen [a Harvard cell biologist who was not involved with the study] says. “It opens new doors” [Science News].
Although serotonin produced by the gut makes up 95 percent of the body’s serotonin, its function had not been well understood. The connection between serotonin and bone formation revealed itself through two types of rare human diseases, both involving the gene Lrp5. People with one mutation produced less Lrp5 protein, developing fragile bones and blindness, while people with another mutation produced extra Lrp5 protein, developing unusually dense bones and resistance to osteoporosis. However, when the authors of the new study looked into the gene further, they were surprised to find that it acted not in bone cells but in cells of the gut. “We, as bone [researchers], thought of the skeleton as functioning independent of everything else,” said [Cliff Rosen, a bone biologist]. This group “asked the question, ‘could there be other regulators outside the skeleton that are regulating bone?’ and found the answer to be ‘yes.’” [The Scientist].
Using transgenic mice, the researchers showed inactivating Lrp5 caused severe osteoporosis while overactivating Lrp5 led to higher bone mass. Specifically, the researchers learned that Lrp5 blocks conversion of the amino acid tryptophan to serotonin, meaning that they could also change the density of the mice’s bones by adjusting the amount of tryptophan in their diet. Mice with inactivated Lrp5 could still produce normal bones if restricted to a low-tryptophan diet.
Osteoporosis, a disease that causes bone loss, affects 10 million Americans over the age of 50. But most existing treatments only prevent further bone loss without increasing the formation of new bone. The discovery could have enormous implications, osteoporosis experts say, because there is an urgent need for osteoporosis treatments that actually build bone [New York Times]. Since the Lrp5 gene doesn’t affect serotonin production in the brain and serotonin produced in the gut cannot cross the blood-brain barrier, it would be an attractive drug target. Senior author Gerard Karsenty hopes to find a new drug that depresses the gut’s serotonin synthesis and stimulates bone growth in these patients [New York Times].
Image: flickr / caterina