title: Regulatory roles of beta-catenin and AP-1 on osteoprotegerin production in interleukin-1alpha-stimulated periodontal ligament cells.
abstract: BACKGROUND
  Periodontitis is a chronic inflammatory disease characterized by the enhanced expression of inflammatory mediators leading to alveolar bone resorption. Osteoprotegerin (OPG) plays a suppressive role in cytokine-induced osteoclastogenesis. In osteoblasts, OPG expression is upregulated by beta-catenin but downregulated by the transcription factor activator protein-1 (AP-1; c-fos/c-jun). The purpose of this study was to examine the roles of beta-catenin and AP-1 in interleukin-1alpha (IL-1alpha) -induced OPG production in human gingival fibroblasts (hGFs) and periodontal ligament (PDL) cells.
  
  
  METHODS
  Expression of c-fos and c-jun messenger RNA was measured by reverse transcription-polymerase chain reaction and OPG production was analysed by enzyme-linked immunosorbent assay. The nuclear AP-1 activity was quantified using an AP-1 microplate assay. The effect of the Wnt canonical pathway on OPG production was evaluated using small interfering (si) RNA for beta-catenin and the effect of AP-1 on OPG production was evaluated using the AP-1 inhibitor curcumin.
  
  
  RESULTS
  Levels of c-fos messenger RNA and nuclear AP-1 activity were higher in PDL cells than in hGFs. When stimulated with IL-1alpha, PDL cells had significantly higher c-fos expression and lower OPG production compared with hGFs. The siRNA for beta-catenin suppressed the IL-1alpha-induced OPG production in both PDL cells and hGFs, whereas the AP-1 inhibitor curcumin augmented the IL-1alpha-induced OPG production in PDL cells, but not in hGFs.
  
  
  CONCLUSIONS
  The present study suggests that beta-catenin enhances IL-1alpha-induced OPG production in both PDL cells and hGFs, whereas AP-1 suppresses IL-1alpha-induced OPG production in PDL cells. Higher expression of c-fos in PDL cells than in hGFs may implicate a role of PDL cells in alveolar bone resorption in periodontitis.
authors.affiliation: Section of Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. suda.peri@tmd.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Suda
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
authors.forename: N
authors.initials: N
authors.lastname: Wara-Aswapati
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Iwasaki
authors.forename: R
authors.initials: R
authors.lastname: Yashiro
authors.forename: D
authors.initials: D
authors.lastname: Hormdee
authors.forename: H
authors.initials: H
authors.lastname: Nitta
authors.forename: I
authors.initials: I
authors.lastname: Ishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Izumi
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D053582:Interleukin-1alpha / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects; D053244:Osteoprotegerin / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D055815:Young Adult; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: C495270:CTNNB1 protein, human; D004791:Enzyme Inhibitors; D053582:Interleukin-1alpha; D053244:Osteoprotegerin; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D051176:beta Catenin; D003474:Curcumin