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Journal of Cellular Biochemistry

Tunneling nanotube formation is essential for the regulation of osteoclastogenesis

Authors

  • Akira Takahashi,

    1. Division of Oral Biological Sciences, Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan
    2. Division of Oral Rehabilitation, Faculty of Dental Science, Section of Implant & Rehabilitative Dentistry, Kyushu University, Maidashi Fukuoka 812-8582, Japan
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  • Akiko Kukita,

    Corresponding author
    1. Division of Biodefense, Department of Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
    • Division of Biodefense, Department of Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
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  • Yin-ji Li,

    1. Division of Oral Biological Sciences, Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan
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  • Jing-qi Zhang,

    1. Division of Oral Biological Sciences, Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan
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  • Hisayuki Nomiyama,

    1. Department of Molecular Enzymology, Kumamoto University Graduate School of Medical Science, Kumamoto 860-8556, Japan
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  • Takayoshi Yamaza,

    1. Division of Oral Biological Sciences, Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan
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  • Yasunori Ayukawa,

    1. Division of Oral Rehabilitation, Faculty of Dental Science, Section of Implant & Rehabilitative Dentistry, Kyushu University, Maidashi Fukuoka 812-8582, Japan
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  • Kiyoshi Koyano,

    1. Division of Oral Rehabilitation, Faculty of Dental Science, Section of Implant & Rehabilitative Dentistry, Kyushu University, Maidashi Fukuoka 812-8582, Japan
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  • Toshio Kukita

    Corresponding author
    1. Division of Oral Biological Sciences, Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan
    • Division of Oral Biological Sciences, Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dental Science, Kyushu University, 3-1-1 Miadashi, Fukuoka 812-8582, Japan.
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  • The authors declared they have no conflict of interest.

Abstract

Osteoclasts are the multinucleated giant cells formed by cell fusion of mononuclear osteoclast precursors. Despite the finding of several membrane proteins involving DC-STAMP as regulatory proteins required for fusion among osteoclast precursors, cellular and molecular events concerning this process are still ambiguous. Here we identified Tunneling Nanotubes (TNTs), long intercellular bridges with small diameters, as the essential cellular structure for intercellular communication among osteoclast precursors in prior to cell fusion. Formation of TNTs was highly associated with osteoclastogenesis and it was accompanied with the significant induction of the M-Sec gene, an essential gene for TNT formation. M-Sec gene expression was significantly upregulated by RANKL-treatment in osteoclast precursor cell line. Blockage of TNT formation by Latrunclin B or by M-Sec siRNA significantly suppressed osteoclastogenesis. We have detected the rapid intercellular transport of not only the membrane phospholipids labeled with DiI but also the DC-STAMP-GFP fusion protein through TNTs formed among osteoclast precursors during osteoclastogenesis. Transportation of such regulatory molecules through TNTs would be essential for the process of the specific cell fusion among osteoclast precursors. J. Cell. Biochem. 114: 1238–1247, 2013. © 2012 Wiley Periodicals, Inc.

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