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Osteoclastogenesis is Influenced by Modulation of Gap Junctional Communication with Antiarrhythmic Peptides

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Abstract

Osteoclasts are formed by the fusion of mononuclear precursor cells of the monocyte–macrophage lineage. Among several putative mechanisms, gap-junctional intercellular communication (GJC) has been proposed to have a role in osteoclast fusion and bone resorption. We examined the role of GJC in osteoclastogenesis and in vitro bone resorption with mouse bone marrow hematopoietic stem cells and RAW 264.7 cells. Blocking of gap junctions with 18-α-glycyrrhetinic acid (18GA) led to inhibition of osteoclastogenesis and in vitro bone resorption. Similarly, the GJC inhibitor GAP27 inhibited osteoclast formation. GJC modulation with the antiarrhythmic peptides (AAPs) led to increased amounts of multinuclear RAW 264.7 osteoclasts as well as increased number of nuclei per multinuclear cell. In the culture of bone marrow hematopoietic stem cells in the presence of bone marrow stromal cells AAP reduced the number of osteoclasts, and coculture of MC3T3-E1 preosteoblasts with RAW 264.7 macrophages prevented the action of AAPs to promote osteoclastogenesis. The present data indicate that AAPs modulate the fusion of the pure culture of cells of the monocyte–macrophage lineage. However, the fusion is influenced by GJC in cells of the osteoblast lineage.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland

    Elina Kylmäoja, Hanna Kokkonen, Kyösti Kauppinen & Juha Tuukkanen

  2. Institute of Anatomy, Chair of Histology and Embryology, University of Tartu, Tartu, Estonia

    Piret Hussar

  3. Department of Anatomy (Division II), Tsurumi University School of Dental Medicine, Tsurumi 2-1-3, Tsurumi-Ku, Yokohama, 230-8501, Japan

    Tetsuji Sato

  4. Department of Cardiology, Roskilde University Hospital, Roskilde, Denmark

    Ketil Haugan

  5. Zealand Pharma A/S, Glostrup, Copenhagen, Denmark

    Bjarne Due Larsen

Authors
  1. Elina Kylmäoja
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  2. Hanna Kokkonen
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  3. Kyösti Kauppinen
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  8. Juha Tuukkanen
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Correspondence to Juha Tuukkanen.

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The authors have stated that they have no conflict of interest.

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Kylmäoja, E., Kokkonen, H., Kauppinen, K. et al. Osteoclastogenesis is Influenced by Modulation of Gap Junctional Communication with Antiarrhythmic Peptides. Calcif Tissue Int 92, 270–281 (2013). https://doi.org/10.1007/s00223-012-9680-8

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  • DOI: https://doi.org/10.1007/s00223-012-9680-8

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