Objectives: The mechanisms of regional acceleratory phenomenon (RAP) induced by orthognathic osteotomy are unclear. It was not known if locally hypoxic microenvironment changes were involved in this phenomenon.
Methods: Hypoxia-induced factor-1α knockout mice harboring Cathepsin K (CTSK) Cre were used to investigate the effect of hypoxia-driven osteoclasts on alveolar bone remodeling. RAW264.7 cells were induced by CoCl to observe the effects of dendritic cell-specific transmembrane protein (DC-STAMP) on the fusion and differentiation of osteoclasts.
Results: We found mandibular osteotomy of C57 mice induced active alveolar osteoclasts and increased hypoxia-induced factor-1α (HIF-1α) positive staining areas. Alveolar bone density of the 10-week-old HIF-1α conditional knockout (CKO) mouse was increased at 10 and 14 days after bilateral mandibular osteotomy. Moreover, decreased numbers of osteoclasts and matrix metalloproteinase 9 (MMP-9)-positive cells were observed on the surface of bone resorption lacunae in the CKO group. HIF-1α could increase the expression level of DC-STAMP to enhance osteoclastogenesis and cell fusion in active RAW264.7 cells.
Conclusion: Our data considered hypoxia-driven osteoclasts resorption to be an adaptive mechanism to permit alveolar bone loss after bilateral mandibular osteotomy of mice.
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