Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in Periodontal Ligament Fibroblasts

摘要: During orthodontic tooth movement, local hypoxia and enhanced osteoclastogenesis are observed in the compression side of periodontal tissues. The receptor activator nuclear factor-κB ligand (RANKL) is an osteoblast/stromal cell-derived factor that essential for osteoclastogenesis. In this study, we examined effect on RANKL expression human ligament fibroblasts (PDLFs) to investigate relationship between Hypoxia significantly levels mRNA protein as well inducible factor-1α (HIF-1α) PDLFs. Constitutively active HIF-1α alone increased PDLFs under normoxic conditions, whereas dominant negative blocked hypoxia-induced expression. To further whether directly regulates transcription, a luciferase reporter assay was performed using vector containing promoter sequence. Exposure or overexpression constitutively activity, activity. Furthermore, mutations putative binding elements prevented results chromatin immunoprecipitation showed DNA promoter. These suggest mediates up-regulation ligament, enhances osteoclastogenesis, at least part, via