Hypoxia-induced factor 1α promotes osteotomy-induced regional acceleratory phenomenon via DC-STAMP mediated membrane fusion.

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 CoCl2 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.