The serotonin 5‐HT 2B receptor controls bone mass via osteoblast recruitment and proliferation

ABSTRACT The monoamine serotonin (5‐HT), a well‐known neurotransmitter, is also important in peripheral tissues. Several studies have suggested that 5‐HT is involved in bone metabolism. Starting from our original observation of increased 5‐HT 2B receptor (5‐HT 2B R) expression during in vitro osteoblast differentiation, we investigated a putative bone phenotype in vivo in 5‐HT 2B R knockout mice. Of interest, 5‐HT 2B R mutant female mice displayed reduced bone density that was significant from age 4 months and had intensified by 12 and 18 months. This histomorphometrically confirmed osteopenia seems to be due to reduced bone formation because 1 ) the alkaline phosphatase‐positive colony‐forming unit capacity of bone marrow precursors was markedly reduced in the 5‐HT 2B R mutant mice from 4 to 12 months of age, 2 ) ex vivo primary osteo‐blasts from mutant mice exhibited reduced proliferation and delayed differentiation, and 3 ) calcium incorporation was markedly reduced in osteoblasts after 5‐HT 2B R depletion (produced genetically or by pharmacological inactivation). These findings support the hypothesis that the 5‐HT 2B R receptor facilitates osteo‐blast recruitment and proliferation and that its absence leads to osteopenia that worsens with age. We show here, for the first time, that the 5‐HT 2B R receptor is a physiological mediator of 5‐HT in bone formation and, potentially, in the onset of osteoporosis in aging women.—Collet, C., Schiltz, C., Geoffroy, V., Maroteaux, L., Launay, J.‐M., de Vernejoul, M.‐C. The serotonin 5‐HT 2B receptor controls bone mass via osteoblast recruitment and proliferation. FASEB J. 22, 418–427 (2008)