The role of heme oxygenase-1 in mechanical stress- and lipopolysaccharide-induced osteogenic differentiation in human periodontal ligament cells

The role of heme oxygenase-1 in mechanical stress- and lipopolysaccharide-induced osteogenic differentiation in human periodontal ligament cells
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DOI:
10.2319/091509-520.1
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发表时间:
2010-07-01
期刊:
影响因子:
3.4
通讯作者:
Kim, Eun-Cheol
Kim, Eun-Cheol
中科院分区:
医学2区
文献类型:
--
作者:
Cho, Jin-Hyoung;Lee, Sun-Kyung;Kim, Eun-Cheol

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目的:探讨机械应力和内毒素诱导牙周膜细胞向成骨细胞分化的机制。材料与方法:应用FlexWell细胞应变装置对牙周膜细胞进行内毒素和/或机械应变处理。结果:内毒素与机械应变联合作用后,骨形态发生蛋白-2、骨形态发生蛋白-7和Runx2mRNA的表达增加受到抑制,而血红素加氧酶-1的表达进一步增强。此外,用血红素加氧酶-1抑制剂或p38、丝裂原活化蛋白激酶、JNK、磷脂酰肌醇3-激酶、蛋白激酶G和核因子-kappaB的抑制剂预先处理,可抑制脂多糖和机械张力诱导的成骨分化。结论:正畸力诱导的牙槽骨成骨受伴随的牙周炎的抑制,其机制可能是通过上调血红素加氧酶-1的表达。因此,血红素加氧酶-1通路可能为正畸治疗中改善骨形成提供一种可能的治疗策略。(角度直角。2010;80:740-747。)
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.)