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Titolo:
Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand
Autore:
Iwamoto, T; Fukumoto, S; Kanaoka, K; Sakai, E; Shibata, M; Fukumoto, E; Inokuchi, J; Takamiya, K; Furukawa, K; Furukawa, K; Kato, Y; Mizuno, A;
Indirizzi:
Nagasaki Univ, Sch Dent, Dept Pediat Dent, Nagasaki 8528588, Japan Nagasaki Univ Nagasaki Japan 8528588 ediat Dent, Nagasaki 8528588, Japan Nagasaki Univ, Sch Dent, Dept Oral & Maxillofacial Surg 1, Nagasaki 8528588, Japan Nagasaki Univ Nagasaki Japan 8528588 ial Surg 1, Nagasaki 8528588, Japan Nagasaki Univ, Sch Dent, Dept Prevent Dent, Nagasaki 8528588, Japan Nagasaki Univ Nagasaki Japan 8528588 event Dent, Nagasaki 8528588, Japan Nagasaki Univ, Sch Dent, Dept Pharmacol, Nagasaki 8528588, Japan Nagasaki Univ Nagasaki Japan 8528588 Pharmacol, Nagasaki 8528588, Japan Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Biomembrane & Biofunct Chem, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ Sapporo Hokkaido Japan 0600812 oro, Hokkaido 0600812, Japan Nagoya Univ, Sch Med, Dept Biochem 2, Nagoya, Aichi 4660065, Japan Nagoya Univ Nagoya Aichi Japan 4660065 em 2, Nagoya, Aichi 4660065, Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 49, volume: 276, anno: 2001,
pagine: 46031 - 46038
SICI:
0021-9258(200112)276:49<46031:LIEFTO>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTERCELLULAR-ADHESION MOLECULE-1; TYROSINE KINASE-ACTIVITY; GROWTH-FACTOR RECEPTOR; NEURITE OUTGROWTH; BONE-RESORPTION; CELL-ADHESION; GLUCOSYLCERAMIDE SYNTHASE; SIGNAL-TRANSDUCTION; GLYCOSPHINGOLIPID SYNTHESIS; COMPLEX GANGLIOSIDES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Fukumoto, S Nagasaki Univ, Sch Dent, Dept Pediat Dent, 1-7-1 Sakamoto, Nagasaki 8528588, Japan Nagasaki Univ 1-7-1 Sakamoto Nagasaki Japan 8528588 88, Japan
Citazione:
T. Iwamoto et al., "Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand", J BIOL CHEM, 276(49), 2001, pp. 46031-46038

Abstract

Glycosphingolipids and their metabolites play important roles in a varietyof biological processes. Several signal molecules are localized in a glycolipid-enriched microdomain on the cell surface, and their signals are regulated by the glycolipid composition. However, the function of glycolipids inosteoclastogenesis has not been clearly understood. We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanoI (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation inducedby macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappaB ligand (RANKL) in a dose-dependent manner. Expression of RANK, the receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced markedly in D-PDMP-treated cells. D-PDMP also inhibited the phosphorylation. of the inhibitor of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 induced by RANKL. In several experiments with theaddition of glycolipids to D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly affected the differentiation into tartrate-resistant acid phosphatase mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer recovered the reduced expression of RANK and the phosphorylation of inhibitor of NF-kappaB and extracellular signal-regulated kinase 1/2 after stimulation by RANKL at the same level of cells without D-PDMP treatment. Our data suggest that glycosphingolipids, especially LacCer, are necessary for the initiation step of RANKL-induced osteoclastogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/21 alle ore 02:24:41