Transiently increased serotonin has modest or no effects on bone mass accrual in growing female C57BL6/J or growing male and female Lrp5(A214v) mice

Serotonin (5HT) is a chemical messenger with biologic activities affecting multiple organs. Within the skeletal system, studies in mice and humans suggest blood 5HT levels affect bone, with elevations impairing and reductions enhancing bone accrual. Other studies, however, have not supported this hypothesis. Recently, administering 5HT to a Piezo1 mutant mouse strain with hyposerotonemia, intestinal dysmotility, and a doubling of femoral trabecular bone mass at 2 months of age, was reported to return the animals' intestinal motility and bone mass to normal. However, whether the 5HT directly affected bone metabolism or indirectly affected metabolism by improving intestinal function was not determined. Therefore, we administered 5HT to mice with normal intestinal function. We randomized female C57BL6/J mice and male and female mice that have increased bone mass due to a missense mutation in the WNT co-receptor LRP5 (Lrp5(A214v)) to receive 5HT or vehicle via daily IP injection from 4 weeks to 8 weeks of age. We did not observe consistent significant changes for distal femur trabecular, midshaft femur cortical, or vertebral body trabecular bone mass between 5HT treated and vehicle treated mice of either genotype. These data are compatible with other studies that have not observed a correlation between blood 5HT level and bone mass.