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

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概要

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• 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>D</sc>-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (<sc>D</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>D</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>D</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>D</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>D</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.

• 社団法人 日本薬理学会の論文
• 2006-03-20

著者

• Sakai Eiko

  九州大学 歯学部小児口腔医学

• Sakai Eiko

  Division Of Oral Molecular Pharmacology Department Of Developmental And Reconstructive Medicine Naga

• 山田 亜矢

  東北大学 歯学研究科小児発達歯科学分野

• Fukumoto Satoshi

  九州大学 歯学部小児口腔医学

• Sakai H

  Osaka Univ. Osaka

• Sakai Eiko

  Howard Hughes Medical Institute The Children's Hospital

• FUKUMOTO Satoshi

  Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental S

• IWAMOTO Tsutomu

  Division of Oral Molecular Pharmacology, Department of Developmental and Reconstructive Medicine, Na

• YUASA Kenji

  Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental S

• FUKUMOTO Emiko

  Division of Oral Health Services Research, Department of Public Health, Nagasaki University Graduate

• YAMADA Aya

  Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental S

• HASEGAWA Tomokazu

  Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental S

• NONAKA Kazuaki

  Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental S

• KATO Yuzo

  Division of Oral Molecular Pharmacology, Department of Developmental and Reconstructive Medicine, Na

• Yamamoto Kenji

  Proteolysis Research Laboratory Graduate School Of Pharmaceutical Sciences Kyushu University

• Fukumoto Satoshi

  Section Of Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Scie

• Fukumoto Satoshi

  Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Science Kyushu

• Sakamoto Hironori

  Department Of Material Physics Faculty Of Engineering Science Osaka University

• Kato Yuzo

  Division Of Oral Molecular Pharmacology Department Of Developmental And Reconstructive Medicine Naga

• Yamada Aya

  Section Of Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Scie

• Hasegawa Tomokazu

  Section Of Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Scie

• Sakai Eri

  Division Of Oral Molecular Pharmacology Department Of Developmental And Reconstructive Medicine Naga

• Kato Yuzo

  Division Of Oral Molecular Pharmacology Department Of Development And Reconstructive Medicine Gradua

• Nonaka Kazuaki

  Section Of Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Scie

• Nonaka Kazuaki

  Section Of Pediatric Dentistry Division Of Oral Health Growth & Development Faculty Of Dental Sc

• Yuasa Kenji

  Section Of Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Scie

• Yuasa Kenji

  Section Of Image Diagnostics Department Of Diagnostics & General Care Department Of Oral & M

• Sakamoto H

  Santen Pharmaceutical Co. Ltd. Developmental Research Division

• Iwamoto Tsutomu

  Section Of Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Scie

• Fukumoto S

  Division Of Pediatric Dentistry Department Of Oral Health And Development Sciences Tohoku University

• Fukumoto Emiko

  Division Of Oral Health Services Research Department Of Public Health Nagasaki University Graduate S

• Iwamoto Tsutomu

  Section Of Pediatric Dentistry Division Of Oral Health Growth And Development Faculty Of Dental Scie

• Sakai Eiko

  Division Of Oral Molecular Pharmacology Department Of Developmental And Reconstructive Medicine Naga

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