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Serotonin Production in Gut Controls Bone Formation

Gene controls serotonin production in gut

FRIDAY, Nov. 28 (HealthDay News) -- A gene that controls the production of serotonin in the gut is an important regulator of bone formation, according to a study in the Nov. 28 issue of Cell.

Vijay K. Yadav, Ph.D., from Columbia University in New York City, and colleagues investigated the function of the LDL-receptor related protein 5 (Lrp5) gene, which had been implicated in the regulation of bone formation because mutations in the gene cause osteoporosis pseudoglioma and high bone mass syndrome.

The researchers found that bones lacking the Lrp5 gene had high expression of the Tph1 gene, which encoded an enzyme that synthesized serotonin in the enterochromaffin cells of the duodenum. Reducing serotonin levels in the blood of Lrp5-deficient mice restored normal bone formation and bone mass, while inactivating Lrp5 in the gut, but not in osteoblasts, reduced bone formation, the investigators report. Gut-specific activation of Lrp5 or inactivation of Tph1 increased bone mass and prevented bone loss in ovariectomized mice. Serotonin inhibited the proliferation of osteoblasts, according to the study.

"By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study broadens our understanding of bone remodeling and suggests potential therapies to increase bone mass," Yadav and colleagues conclude.

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