Regulatory mechanism of expression of ODF and OCIF genes in P.gingivalis LPS-induced bone resorption.

点击翻译按钮获取中文摘要

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.