Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin
Morten Frost, Tom Erenskjold Andersen, Vijay Yadav, Kim Brixen, Gerard Karsenty, Moustapha Kassem, Morten Frost, Tom Erenskjold Andersen, Vijay Yadav, Kim Brixen, Gerard Karsenty, Moustapha Kassem
Abstract
The Lrp5 gene is a major determinant of bone mass accrual. It has been demonstrated recently to achieve this function by hampering the synthesis of gut-derived serotonin, which is a powerful inhibitor of bone formation. In this study we analyzed plasma serotonin levels in patients with a high-bone-mass (HBM) phenotype owing to gain-of-function mutation of Lrp5 (T253I). A total of 9 HBM patients were compared with 18 sex- and age-matched controls. In HBM patients, the serotonin concentrations in platelet-poor plasma were significantly lower than in the controls (mean +/- SEM: 2.16 +/- 0.28 ng/mL versus 3.51 +/- 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans.
Copyright 2010 American Society for Bone and Mineral Research.
Source: PubMed