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Serotonin and fluoxetine receptors are expressed in enamel organs and LS8 cells and modulate gene expression in LS8 cells

Authors

  • Elisabeth A. Riksen,

    1. Department of Biomaterials, Faculty of Dentistry, University of Oslo, Oslo, Norway
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  • Astrid K. Stunes,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, (NTNU), Trondheim, Norway
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  • Anne Kalvik,

    1. Department of Biomaterials, Faculty of Dentistry, University of Oslo, Oslo, Norway
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  • Björn I. Gustafsson,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, (NTNU), Trondheim, Norway
    2. Departments of Gastroenterology and Endocrinology, St Olav’s University Hospital, Trondheim, Norway
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  • Malcolm L. Snead,

    1. Centre for Craniofacial Molecular Biology, The Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
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  • Unni Syversen,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, (NTNU), Trondheim, Norway
    2. Departments of Gastroenterology and Endocrinology, St Olav’s University Hospital, Trondheim, Norway
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  • Ståle P. Lyngstadaas,

    1. Department of Biomaterials, Faculty of Dentistry, University of Oslo, Oslo, Norway
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  • Janne E. Reseland

    1. Department of Biomaterials, Faculty of Dentistry, University of Oslo, Oslo, Norway
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Janne E. Reseland, Department of Biomaterials, Faculty of Dentistry, PO Box 1109 Blindern, N-0317 Oslo, Norway

Telefax: +47–2–2852351
E-mail: j.e.reseland@odont.uio.no

Abstract

Riksen EA, Stunes AK, Kalvik A, Gustafsson BI, Snead ML, Syversen U, Lyngstadaas SP, Reseland JE. Serotonin and fluoxetine receptors are expressed in enamel organs and LS8 cells and modulate gene expression in LS8 cells.
Eur J Oral Sci 2010; 118: 566–573. © 2010 Eur J Oral Sci

The selective serotonin re-uptake inhibitor (SSRI) fluoxetine is widely used in the treatment of depression in children and fertile women, but its effect on developing tissues has been sparsely investigated. The aim of this study was to investigate if enamel organs and ameloblast-derived cells express serotonin receptors that are affected by peripherally circulating serotonin or fluoxetine. Using RT-PCR and western blot analysis we found that enamel organs from 3-d-old mice and ameloblast-like cells (LS8 cells) express functional serotonin receptors, the rate-limiting enzyme in serotonin synthesis (Thp1), as well as the serotonin transporter (5HTT), indicating that enamel organs and ameloblasts are able to respond to serotonin and regulate serotonin availability. Fluoxetine and serotonin enhanced the alkaline phosphatase activity in the cell culture medium from cultured LS8 cells, whereas the expression of enamelin (Enam), amelogenin (Amel), and matrix metalloproteinase-20 (MMP-20) were all significantly down-regulated. The secretion of vascular endothelial growth factor (VEGF), monocyte chemotactic protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10) was also reduced compared with controls. In conclusion, enamel organs and ameloblast-like cells express functional serotonin receptors. Reduced transcription of enamel proteins and secretion of vascular factors may indicate possible adverse effects of fluoxetine on amelogenesis.

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