SEARCH

SEARCH BY CITATION

Keywords:

  • osteoclastogenesis;
  • interferon-γ;
  • lipopolysaccharide;
  • bone resorption

Ayon Haro ER, Ukai T, Yokoyama M, Kishimoto T, Yoshinaga Y, Hara Y. Locally administered interferon-γ accelerates lipopolysaccharide-induced osteoclastogenesis independent of immunohistological RANKL upregulation. J Periodont Res 2011; 46: 361–373. © 2011 John Wiley & Sons A/S

Background and Objective:  Interferon-γ (IFN-γ) potently inhibits RANKL-induced osteoclastogenesis in vitro. In contrast, previous studies have shown that an increase in IFN-γ expression is correlated with an increase in lipopolysaccharide (LPS)-induced bone loss in vivo. However, it is not clear whether local IFN-γ accelerates osteoclastogenesis or not in vivo. Therefore, the aim of this study was to clarify the role of local IFN-γ in LPS-induced osteoclastogenesis.

Material and Methods:  We induced bone loss in calvaria by injecting LPS. One group of mice received an IFN-γ injection together with LPS injection, while another group received IFN-γ 2 d after LPS injection. Bone resorption was observed histologically. Next, we stimulated murine bone marrow macrophages with macrophage-colony stimulating factor and RANKL in vitro. We added different doses of IFN-γ and/or LPS at 0 or 48 h time points. Cells were stained with tartrate-resistant acid phosphatase at 72 h.

Results:  Local administration of IFN-γ together with LPS injection did not affect osteoclast formation. However, IFN-γ injected after LPS injection accelerated osteoclast formation. Also, we confirmed that IFN-γ added at 0 h inhibited RANKL-induced osteoclastogenesis in vitro. However, inhibition by IFN-γ added at 48 h was reduced compared with that by IFN-γ added at 0 h. Interestingly, IFN-γ together with a low concentration of LPS accelerated osteoclast formation when both were added at 48 h compared with no addition of IFN-γ.

Conclusion:  The results suggest that local IFN-γ accelerates osteoclastogenesis in certain conditions of LPS-induced inflammatory bone loss.