2000 Fiscal Year Final Research Report Summary
Regulatory mechanism of expression of ODF and OCIF genes in P.gingivalis LPS-induced bone resorption.
| Project/Area Number |
11671810
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Meikai University |
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Principal Investigator |
AMANO Shigeru Meikai Univ., Dentistry, Associate Prof., 歯学部, 助教授 (90167958)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Kazuyuki Meikai Univ., Dentistry, Assistant, 歯学部, 助手 (20271231)
MIYATA Takashi Meikai Univ., Dentistry, Prof., 歯学部, 教授 (10146251)
KIKUTI Hirotaka Meikai Univ., Dentistry, Assistant, 歯学部, 助手 (70234193)
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| Project Period (FY) |
1999 – 2000
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| Keywords | LPS / IL-6 / ODF / OCIF / CD14 / TLR4 |
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| Research Abstract |
Lipopolysaccharid (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions, and one of these roles is a powerful stimulator of bone resorption. We have shown that endogenous CD14 plays an important role in LPS-stimulated bone resorption that is mediatedby IL-1β and IL-6 induced by the toxin. However, the mechanism by which LPS stimulates bone resorption is not yet understood. In the present study, we show using ST-2 cells having a supporting ability of osteoclast formation that LPS-induced osteoclast differentiation factor (ODF) gene expression in ST-2 cells is mediated by endogenous IL-6 via CD14-TLR4. We observed that LPS obviously stimulated expression of ODF gene in ST-2 cells. The LPS-induced expression of ODF gene was markedly neutralized by anti-mouse IL-6 antibody treatment. In addition, IL-6 was able to induce expression of ODF gene in ST-2 cells. These observations suggest that LPS-induced expression of ODF gene in ST-2 cells was mediated by indirect action of endogenous IL-6. On the other hand, ST-2 cells exhibited constitutive expression of CD14 and Toll-like receptor 4. The LPS-induced expression of IL-6 gene was clearly inhibited by PI-PLC treatment which was an enzyme from B.cereus which specifically cleaves the GPI anchor of CD14. In addition, LPS induction of ODF and IL-6 gene expressions was clearly stimulated in the TLR4-overexpressed ST-2 cells. These results suggested the functional role of CD14 and TLR4 in LPS responsibility of ST-2 cells. The present study thus clearly demonstrates a functional role of endogenous IL-6 via CD14-TLR4 signaling in LPS-stimulated expression of ODF gene.
In conclusion, our present study suggests that LPS induce expression of ODF/RANKL/TRANCE/OPGL gene in mouse stromal ST-2 cells via CD14-TLR4 dependent endogenous IL-6.
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