title: Locally administered interferon-γ accelerates lipopolysaccharide-induced osteoclastogenesis independent of immunohistological RANKL upregulation.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The results suggest that local IFN-γ accelerates osteoclastogenesis in certain conditions of LPS-induced inflammatory bone loss.
authors.affiliation: Unit of Translational Medicine, Course of Medical and Dental Sciences, Department of Periodontology, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: E R
authors.initials: ER
authors.lastname: Ayon Haro
authors.forename: T
authors.initials: T
authors.lastname: Ukai
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshinaga
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004926:Escherichia coli; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D007527:Isoenzymes / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000187:drug effects*; D053245:RANK Ligand / Q000187:drug effects* / Q000494:pharmacology; D012886:Skull / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D008070:Lipopolysaccharides; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase