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

Yi Tang, Xinzhao Li, Yun Cai, Miaomiao Bie, Yuanye Tian, Qi Shao, Feiwu Kang

Oral diseases 2023 Jul

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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. 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. 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. Our data considered hypoxia-driven osteoclasts resorption to be an adaptive mechanism to permit alveolar bone loss after bilateral mandibular osteotomy of mice. © 2022 Wiley Periodicals LLC.

Citation

Yi Tang, Xinzhao Li, Yun Cai, Miaomiao Bie, Yuanye Tian, Qi Shao, Feiwu Kang. Hypoxia-induced factor 1α promotes osteotomy-induced regional acceleratory phenomenon via DC-STAMP mediated membrane fusion. Oral diseases. 2023 Jul;29(5):2139-2153