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Journal of Cellular Biochemistry

Serotonin and fluoxetine modulate bone cell function in vitro

Authors

  • B.I. Gustafsson,

    Corresponding author
    1. Department of Internal Medicine, Sections for Gastroenterology and Endocrinology, St Olavs University Hospital HF, Trondheim, Norway
    2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
    • St Olavs Hospital HF, Medisinsk avdeling, gastroseksjon, N-7006 Trondheim, Norway.
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  • L. Thommesen,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
    2. SørTrøndelag University College, Faculty of Technology, Trondheim, Norway
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  • A.K. Stunes,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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  • K. Tommeras,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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  • I. Westbroek,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
    2. Departments of Internal Medicine and Orthopaedics, Erasmus MC, Rotterdam, The Netherlands
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  • H.L. Waldum,

    1. Department of Internal Medicine, Sections for Gastroenterology and Endocrinology, St Olavs University Hospital HF, Trondheim, Norway
    2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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  • K. Slørdahl,

    1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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  • M.V. Tamburstuen,

    1. Oral Research Laboratory, Faculty of Dentistry, University of Oslo, N-0316 Oslo, Norway
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  • J.E. Reseland,

    1. Oral Research Laboratory, Faculty of Dentistry, University of Oslo, N-0316 Oslo, Norway
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  • U. Syversen

    1. Department of Internal Medicine, Sections for Gastroenterology and Endocrinology, St Olavs University Hospital HF, Trondheim, Norway
    2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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Abstract

Recent studies have proposed a role for serotonin and its transporter in regulation of bone cell function. In the present study, we examined the in vitro effects of serotonin and the serotonin transporter inhibitor fluoxetine “Prozac” on osteoblasts and osteoclasts. Human mononuclear cells were differentiated into osteoclasts in the presence of serotonin or fluoxetine. Both compounds affected the total number of differentiated osteoclasts as well as bone resorption in a bell-shaped manner. RT-PCR on the human osteoclasts demonstrated several serotonin receptors, the serotonin transporter, and the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Tph1 expression was also found in murine osteoblasts and osteoclasts, indicating an ability to produce serotonin. In murine pre-osteoclasts (RAW264.7), serotonin as well as fluoxetine affected proliferation and NFκB activity in a biphasic manner. Proliferation of human mesenchymal stem cells (MSC) and primary osteoblasts (NHO), and 5-HT2A receptor expression was enhanced by serotonin. Fluoxetine stimulated proliferation of MSC and murine preosteoblasts (MC3T3-E1) in nM concentrations, µM concentrations were inhibitory. The effect of fluoxetine seemed direct, probably through 5-HT2 receptors. Serotonin-induced proliferation of MC3T3-E1 cells was inhibited by the PKC inhibitor (GF109203) and was also markedly reduced when antagonists of the serotonin receptors 5-HT2B/C or 5-HT2A/C were added. Serotonin increased osteoprotegerin (OPG) and decreased receptor activator of NF-κB ligand (RANKL) secretion from osteoblasts, suggesting a role in osteoblast-induced inhibition of osteoclast differentiation, whereas fluoxetine had the opposite effect. This study further describes possible mechanisms by which serotonin and the serotonin transporter can affect bone cell function. J. Cell. Biochem. 98: 139–151, 2006. © 2006 Wiley-Liss, Inc.

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