Current Topics in Pharmacological Research on Bone Metabolism : Osteoclast Differentiation Regulated by Glycosphingolipids

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Author(s)

    • Iwamoto Tsutomu IWAMOTO Tsutomu
    • Division of Oral Molecular Pharmacology, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences
    • Sakai Eiko [他] SAKAI Eiko
    • Division of Oral Molecular Pharmacology, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences
    • YUASA Kenji
    • Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University
    • FUKUMOTO Emiko
    • Division of Oral Health Services Research, Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences
    • YAMADA Aya
    • Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University
    • HASEGAWA Tomokazu
    • Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University
    • NONAKA Kazuaki
    • Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University
    • KATO Yuzo
    • Division of Oral Molecular Pharmacology, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences

Abstract

Glycosphingolipids are thought to play important roles in the development and function of several tissues, although the function of glycolipids in osteoclastogenesis has not been clearly demonstrated. In the present study, <sc><font size = "-2">D</font></sc>-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (<sc><font size = "-2">D</font></sc>-PDMP), a glucosylceramide synthase inhibitor, completely inhibited osteoclastogenesis induced by macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). Following treatment with <sc><font size = "-2">D</font></sc>-PDMP, nearly all glycosphingolipid expression was dramatically reduced on the surface of bone marrow cells, which suggests that glycosphingolipids are necessary for osteoclastogenesis. To determine which kinds of glycolipids are important for osteoclastogenesis, we added several types of purified glycolipids to <sc><font size = "-2">D</font></sc>-PDMP treated bone marrow cells, as the precursor of osteoclasts is known to express glucosylceramide (GlcCer) and lactosylceramide (LacCer). Following treatment with RANKL, ganglioside GM3 and GM1 were increased in the treated bone marrow cells, whereas other types were not detected using thin layer chromatography analysis. In cells cultured with those glycolipids, exogenously added LacCer rescued osteoclastogenesis blocking by <sc><font size = "-2">D</font></sc>-PDMP. Furthermore, receptor activator of nuclear factor κB (RANK) induced the recruitment of tumor necrosis factor (TNF)-associated factors 2 and 6 (TRAF2 and 6, respectively) to the cytoplasmic tail of RANKL with activated IκB kinase and IκB phosphorylation, while <sc><font size = "-2">D</font></sc>-PDMP treatment inhibited RANKL and induced IκB phosphorylation, and that inhibition was recovered by LacCer. In addition, RANK, TRAF2, TRAF6, and LacCer were found localized in lipid rafts on the cell surfaces. These results suggest that glycosphingolipids, especially LacCer, are important for the initial step of RANKL-induced osteoclastogenesis via lipid rafts.<br>

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 100(3), 195-200, 2006-03-20

    The Japanese Pharmacological Society

References:  29

Cited by:  1

Codes

  • NII Article ID (NAID)
    10018240300
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13478613
  • NDL Article ID
    7858207
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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