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. Materials and 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 kappa B 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. (Angle Orthod. 2010;80:740-747.)