Locally administered interferon-γ accelerates lipopolysaccharide-induced osteoclastogenesis independent of immunohistological RANKL upregulation
Article first published online: 1 MAR 2011
© 2011 John Wiley & Sons A/S.
Journal of Periodontal Research
Volume 46, Issue 3, pages 361–373, June 2011
How to Cite
Ayon Haro, E. R., Ukai, T., Yokoyama, M., Kishimoto, T., Yoshinaga, Y. and Hara, Y. (2011), Locally administered interferon-γ accelerates lipopolysaccharide-induced osteoclastogenesis independent of immunohistological RANKL upregulation. Journal of Periodontal Research, 46: 361–373. doi: 10.1111/j.1600-0765.2011.01352.x
- Issue published online: 18 APR 2011
- Article first published online: 1 MAR 2011
- Accepted for publication December 22, 2010
- 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.