title: The role of heme oxygenase-1 in mechanical stress- and lipopolysaccharide-induced osteogenic differentiation in human periodontal ligament cells.
abstract: OBJECTIVE
  To investigate the mechanisms through which mechanical stress and lipopolysaccharide treatment modulate osteoblastic differentiation in periodontal ligament cells.
  
  
  METHODS
  Cells were treated with lipopolysaccharide and/or mechanical strain applied with a Flexercell Strain Unit. Protein expression and mRNA were analyzed by Western blotting and reverse transcription-polymerase chain reaction, respectively.
  
  
  RESULTS
  When lipopolysaccharide was co-applied with mechanical strain, the increase in the expression of bone morphogenetic protein-2, bone morphogenetic protein-7, and Runx2 mRNA seen with mechanical strain alone was restricted, but heme oxygenase-1 expression was further enhanced. Furthermore, pretreatment with an inhibitor of heme oxygenase-1 or inhibitors of p38, mitogen-activated protein kinase, JNK, phosphoinositide 3-kinases, protein kinase G, and nuclear factor kappaB restricted osteogenic differentiation induced by the application of lipopolysaccharide and mechanical strain.
  
  
  CONCLUSIONS
  These results suggest that orthodontic force-induced osteogenesis in alveolar bone is inhibited by the accompanying periodontal inflammation via the upregulation of heme oxygenase-1 expression. Thus, the heme oxygenase-1 pathway could provide a possible therapeutic strategy to improve bone formation in orthodontic treatment.
authors.affiliation: Department of Orthodontics, Wonkwang University, Iksan, South Korea.
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Cho
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000539:Alveolar Process / Q000201:enzymology*; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D003799:Dental Stress Analysis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology* / Q000201:enzymology; D013314:Stress, Mechanical; D014087:Tooth Movement Techniques; D015854:Up-Regulation
chemical_list: D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D050659:Core Binding Factor Alpha 1 Subunit; D008070:Lipopolysaccharides; C493709:RUNX2 protein, human; D051547:Heme Oxygenase-1