The role of heme oxygenase-1 in mechanical stress- and lipopolysaccharide-induced osteogenic differentiation in human periodontal ligament cells.
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.
Cho
Jin-Hyoung
JH
Department of Orthodontics, Wonkwang University, Iksan, South Korea.
Lee
Sun-Kyung
SK
Lee
Jin-Woo
JW
Kim
Eun-Cheol
EC
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
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