Locally administered interferon-γ accelerates lipopolysaccharide-induced osteoclastogenesis independent of immunohistological RANKL upregulation

Background and Objective: Interferon-gamma (IFN-gamma) potently inhibits RANKL-induced osteoclastogenesis in vitro. In contrast, previous studies have shown that an increase in IFN-gamma expression is correlated with an increase in lipopolysaccharide (LPS)-induced bone loss in vivo. However, it is not clear whether local IFN-gamma accelerates osteoclastogenesis or not in vivo. Therefore, the aim of this study was to clarify the role of local IFN-gamma in LPS-induced osteoclastogenesis. Material and Methods: We induced bone loss in calvaria by injecting LPS. One group of mice received an IFN-gamma injection together with LPS injection, while another group received IFN-gamma 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-gamma 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-gamma together with LPS injection did not affect osteoclast formation. However, IFN-gamma injected after LPS injection accelerated osteoclast formation. Also, we confirmed that IFN-gamma added at 0 h inhibited RANKL-induced osteoclastogenesis in vitro. However, inhibition by IFN-gamma added at 48 h was reduced compared with that by IFN-gamma added at 0 h. Interestingly, IFN-gamma together with a low concentration of LPS accelerated osteoclast formation when both were added at 48 h compared with no addition of IFN-gamma. Conclusion: The results suggest that local IFN-gamma accelerates osteoclastogenesis in certain conditions of LPS-induced inflammatory bone loss.