Expression of Hypoxia-inducible Factor in Periodontal Cells by Orthodontic Forces

Objectives: Osteoclastic bone resorption occurs at sites of compression during orthodontic tooth movement; however, the mechanism by which blood vessels are induced to provide osteoclast precursors at these sites is unknown. To determine whether orthodontic forces promote periodontal angiogenesis, we investigated the expression of hypoxia-inducible factor-1alpha (HIF-1α), which is activated under hypoxic conditions and promotes the expression of vascular endothelial growth factor (VEGF) during the application of orthodontic forces. Methods: Orthodontic forces were applied between the first and second upper molars in rats by the insertion of elastic bands. Human periodontal ligament (HPDL) cells were loaded by mounting cover glasses onto the cells or by increasing the amount of culture medium. The expression of HIF-1α or VEGF was then examined by immunohistochemistry, semi-quantitative RT-PCR, and ELISA. Results: HIF-1α-immunopositive cells appeared during the initial stages of movement of the rat molars, followed by the appearance of VEGF at sites of compression in the periodontal ligament. After the addition of mechanical stress by mounting cover glasses onto cells, HIF-1α-positive reactions were observed in the nuclei, and the number of HIF-1α-positive cells increased in a load-dependent manner. HIF-1α was constitutively expressed in both the control and experimental groups. VEGF expression was observed in the cells that were loaded for 8 h, and the maximum amount of VEGF secreted from the cells loaded with cover glasses was 1.2-folds greater than that secreted from the controls. Conclusions: HIF-1α appeared first, followed by the induction of VEGF expression in periodontal ligament cells after loading, which may contribute to the formation of new vascular tissue for tooth movement.