HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-9209comv1 22/2/418    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Collet, C. Articles by de Vernejoul, M.-C. PubMed PubMed Citation Articles by Collet, C. Articles by de Vernejoul, M.-C.

The serotonin 5-HT_2B receptor controls bone mass via osteoblast recruitment and proliferation

C. Collet^*,1, C. Schiltz^,1, V. Geoffroy, L. Maroteaux, J.-M. Launay^* and M.-C. de Vernejoul^,2

^* Service de Biochimie, Hôpital Lariboisière, Paris, France;

INSERM U606, Hôpital Lariboisière, Paris, France; and

INSERM U839, Institut du Fer à Moulin, Paris, France.

²Correspondence: INSERM U606 Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris cedex 10, France. E-mail: christine.devernejoul{at}lrb.aphp.fr

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_2BR) expression during in vitro osteoblast differentiation, we investigated a putative bone phenotype in vivo in 5-HT_2BR knockout mice. Of interest, 5-HT_2BR 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_2BR mutant mice from 4 to 12 months of age, 2) ex vivo primary osteoblasts from mutant mice exhibited reduced proliferation and delayed differentiation, and 3) calcium incorporation was markedly reduced in osteoblasts after 5-HT_2BR depletion (produced genetically or by pharmacological inactivation). These findings support the hypothesis that the 5-HT_2BR receptor facilitates osteoblast 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_2BR 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.

Key Words: osteoporosis • aging • neurotransmitter