Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin.
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.
Frost
Morten
M
Department of Endocrinology and Metabolism, Laboratory for Molecular Endocrinology (KMEB), Medical Biotechnology Centre, University of Southern Denmark, Odense, Denmark.
Andersen
Tom Erenskjold
TE
Yadav
Vijay
V
Brixen
Kim
K
Karsenty
Gerard
G
Kassem
Moustapha
M
D000328:Adult; D015519:Bone Density / Q000235:genetics*; D005260:Female; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000378:metabolism*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D009154:Mutation; D010012:Osteogenesis / Q000235:genetics; D010641:Phenotype; D012701:Serotonin / Q000097:blood*
D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D012701:Serotonin