title: Epithelial Cells Secrete Interferon-γ Which Suppresses Expression of Receptor Activator of Nuclear Factor Kappa-B Ligand in Human Mandibular Osteoblast-Like Cells.
abstract: Prostaglandin (PG)E2accumulates in inflamed periodontal tissue and induces receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling associated with bone resorption. Although oral epithelial cells maintain tissue homeostasis, the role of these cells in RANKL regulation remains unknown.
  
  
  
  To mimic an inflamed condition, RANKL upregulation in human mandibular osteoblast-like cells (HMOBs) were stimulated with PGE2. Effect of recombinant human interferon (IFN)-γ or epithelial-derived IFN-γ in constitutively released or Porphyromonas gingivalis lipopolysaccharide (PgLPS)-stimulated epithelial supernatant was investigated in HMOBs. Some HMOBs were pretreated with an anti-IFN-γ antibody before PGE2stimulation. THP-1 human monocytes and HMOBs were cocultured in a transwell system to investigate RANKL-driven THP-1 osteoclastic activity.
  
  
  
  PGE2significantly increased RANKL messenger RNA (mRNA) and protein in HMOBs in a dose-dependent manner, while OPG protein remained similar to baseline. Epithelial cells constitutively released IFN-γ, which was substantially increased by PgLPS. HMOBs treated with epithelial supernatant or recombinant IFN-γ, concurrently with PGE2stimulation, reduced RANKL, but not OPG, expression. In contrast, anti-IFN-γ antibody reversed the effect of epithelial mediators on RANKL expression. When cocultured with THP-1, RANKL released by PGE2-stimulated HMOBs is adequate to drive THP-1 differentiation as osteoclastogenic gene expression and bone resorption pit are increased. However, recombinant IFN-γ, or IFN-γ derived from oral epithelial cells, suppressed RANKL expression at both the mRNA and protein level, resulting in decreased THP-1-derived osteoclastic activity.
  
  
  
  Oral epithelial cells interact with HMOBs by releasing IFN-γ to regulate RANKL expression and contribute to osteoclastogenesis.
authors.affiliation: Research Unit on Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.|Department of Microbiology, Faculty of Dentistry, Chulalongkorn University.|Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University.
authors.forename: Pakchisa
authors.initials: P
authors.lastname: Khonsuphap
authors.affiliation: Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University.|Department of Anatomy, Faculty of Dentistry, Chulalongkorn University.
authors.forename: Prasit
authors.initials: P
authors.lastname: Pavasant
authors.affiliation: Research Unit on Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.|Department of Microbiology, Faculty of Dentistry, Chulalongkorn University.
authors.forename: Rizky Aditya
authors.initials: RA
authors.lastname: Irwandi
authors.affiliation: Department of Preventive Dentistry, Faculty of Dentistry, Prince of Songkla University, Songkla, Thailand.
authors.forename: Chidchanok
authors.initials: C
authors.lastname: Leethanakul
authors.affiliation: Research Unit on Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.|Department of Microbiology, Faculty of Dentistry, Chulalongkorn University.
authors.forename: Anjalee
authors.initials: A
authors.lastname: Vacharaksa
mesh_terms: D015153:Blotting, Western; D015232:Dinoprostone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008334:Mandible / Q000166:cytology; D009061:Mouth Mucosa / Q000166:cytology; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053245:RANK Ligand; D012333:RNA, Messenger; D007371:Interferon-gamma; D015232:Dinoprostone
keywords: Bone remodeling; RANK ligand; bone resorption; epithelial cells; interferon-γ; osteoblast