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Regulation of Bone Metabolism by Serotonin

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Understanding the Gut-Bone Signaling Axis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1033))

Abstract

The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption. Its actions on bone metabolism can vary, based on its site of synthesis (central or peripheral) as well as the cells and subtypes of receptors that are activated. Within the central nervous system, serotonergic neurons act via the hypothalamus to suppress sympathetic input to the bone. Since sympathetic input inhibits bone formation, brain serotonin has a net positive effect on bone growth. Gut-derived serotonin is thought to inhibit bone growth by attenuating osteoblast proliferation via activation of receptors on pre-osteoblasts. There is also evidence that serotonin can be synthesized within the bone and act to modulate bone metabolism. Osteoblasts, osteoclasts, and osteocytes all have the machinery to synthesize serotonin, and they also express the serotonin-reuptake transporter (SERT). Understanding the roles of serotonin in the tightly balanced system of bone modeling and remodeling is a clinically relevant goal. This knowledge can clarify bone-related side effects of drugs that affect serotonin signaling, including serotonin-specific reuptake inhibitors (SSRIs) and receptor agonists and antagonists, and it can potentially lead to therapeutic approaches for alleviating bone pathologies.

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Acknowledgments

Work conducted in the author’s laboratories has been supported by NIH grants DK62267 (to GMM) and R37 DE012528 (to JBL).

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Authors and Affiliations

  1. Department of Neurological Sciences, The University of Vermont, Burlington, VT, 05405, USA

    Brigitte Lavoie & Gary M. Mawe

  2. The University of Vermont, D406 Given Building, Burlington, VT, 05405, USA

    Brigitte Lavoie

  3. Department of Biochemistry, The University of Vermont, Burlington, VT, 05405, USA

    Jane B. Lian

Authors
  1. Brigitte Lavoie
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  2. Jane B. Lian
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  3. Gary M. Mawe
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Correspondence to Brigitte Lavoie .

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Editors and Affiliations

  1. Department of Physiology and Department of Radiology Biomedical Imaging Research Centre, Michigan State University, East Lansing, Michigan, USA

    Laura R. McCabe

  2. Comparative Medicine and Integrative Biology Program, East Lansing, Michigan, USA

    Narayanan Parameswaran

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Lavoie, B., Lian, J.B., Mawe, G.M. (2017). Regulation of Bone Metabolism by Serotonin. In: McCabe, L., Parameswaran, N. (eds) Understanding the Gut-Bone Signaling Axis. Advances in Experimental Medicine and Biology, vol 1033. Springer, Cham. https://doi.org/10.1007/978-3-319-66653-2_3

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