Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via toll-like receptors

T. Kikuchi, T. Matsuguchi, N. Tsuboi, A. Mitani, S. Tanaka, M. Matsuoka, G. Yamamoto, T. Hishikawa, T. Noguchi, Yasunobu Yoshikai

    Research output: Contribution to journalArticle

    170 Citations (Scopus)

    Abstract

    Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing ab of TNF-α and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid a were defective in primary osteoblasts from c3h/hej mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.

    Original languageEnglish
    Pages (from-to)3574-3579
    Number of pages6
    JournalJournal of Immunology
    Volume166
    Issue number5
    DOIs
    Publication statusPublished - Mar 1 2001

    Fingerprint

    RANK Ligand
    Toll-Like Receptors
    Osteoblasts
    Lipopolysaccharides
    Gene Expression
    Messenger RNA
    Extracellular Signal-Regulated MAP Kinases
    Osteoclasts
    Protein Kinase C
    CD14 Antigens
    Toll-Like Receptor 2
    Cell Line
    Toll-Like Receptor 4
    Protein Synthesis Inhibitors
    Macrophage Colony-Stimulating Factor
    Periodontitis
    Cycloheximide
    Stromal Cells
    Prostaglandins E
    Membrane Proteins

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via toll-like receptors. / Kikuchi, T.; Matsuguchi, T.; Tsuboi, N.; Mitani, A.; Tanaka, S.; Matsuoka, M.; Yamamoto, G.; Hishikawa, T.; Noguchi, T.; Yoshikai, Yasunobu.

    In: Journal of Immunology, Vol. 166, No. 5, 01.03.2001, p. 3574-3579.

    Research output: Contribution to journalArticle

    Kikuchi, T, Matsuguchi, T, Tsuboi, N, Mitani, A, Tanaka, S, Matsuoka, M, Yamamoto, G, Hishikawa, T, Noguchi, T & Yoshikai, Y 2001, 'Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via toll-like receptors', Journal of Immunology, vol. 166, no. 5, pp. 3574-3579. https://doi.org/10.4049/jimmunol.166.5.3574
    Kikuchi, T. ; Matsuguchi, T. ; Tsuboi, N. ; Mitani, A. ; Tanaka, S. ; Matsuoka, M. ; Yamamoto, G. ; Hishikawa, T. ; Noguchi, T. ; Yoshikai, Yasunobu. / Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via toll-like receptors. In: Journal of Immunology. 2001 ; Vol. 166, No. 5. pp. 3574-3579.
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    abstract = "Osteoclast differentiation factor (ODF), a recently identified cytokine of the TNF family, is expressed as a membrane-associated protein in osteoblasts and stromal cells. ODF stimulates the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here we investigated the effects of LPS on the gene expression of ODF in mouse osteoblasts and an osteoblast cell line and found that LPS increased the ODF mRNA level. A specific inhibitor of extracellular signal-regulated kinase or protein kinase C inhibited this up-regulation, indicating that extracellular signal-regulated kinase and protein kinase C activation was involved. A protein synthesis inhibitor, cycloheximide, rather enhanced the LPS-mediated increase of ODF mRNA, and both a neutralizing ab of TNF-α and a specific inhibitor of PGE synthesis failed to block the ODF mRNA increase by native LPS. Thus, LPS directly induced ODF mRNA. Mouse osteoblasts and an osteoblast cell line constitutively expressed toll-like receptor (TLR) 2 and 4, which are known as putative LPS receptors. ODF mRNA increases in response to synthetic lipid a were defective in primary osteoblasts from c3h/hej mice that contain a nonfunctional mutation in the TLR4 gene, suggesting that TLR4 plays an essential role in the process. Altogether, our results indicate that ODF gene expression is directly increased in osteoblasts by LPS treatment via TLR, and this pathway may play an important role in the pathogenesis of LPS-mediated bone disorders, such as periodontitis.",
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    AU - Mitani, A.

    AU - Tanaka, S.

    AU - Matsuoka, M.

    AU - Yamamoto, G.

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