双膦酸盐性颌骨坏死小鼠模型中髓系抑制细胞及亚群的变化

The change of myeloid-derived suppressor cells and subsets in bisphosphonate-related osteonecrosis of the jaw of mice

目的:通过建立双膦酸盐性颌骨坏死(BRONJ)小鼠模型,探究髓系抑制细胞(MDSC)改变在BRONJ发病机理中的潜在作用。方法:通过静脉注射唑来膦酸诱导C57BL/6小鼠产生BRONJ样疾病,观察其牙龈愈合情况,micro-CT测量牙槽窝骨质修复情况,组织学检测拔牙窝周围骨质破坏及坏死情况。通过流式细胞术检测小鼠外周血中MDSC及其亚群所占的比例变化。结果:与对照组比较,BRONJ小鼠的拔牙窝黏膜未完全愈合,牙槽窝空虚,micro-CT可见拔牙窝散在高密度影像;HE染色显示骨小梁被吸收,拔牙窝周围可见多核巨细胞破坏骨质。与对照组比较,BRONJ小鼠外周血中MDSC及其亚群的比例明显降低。结论:BRONJ小鼠模型中MDSC分化受到了抑制,从而验证了免疫功能失调导致BRONJ发生的机制。

Objective:To explore the potential role of myeloid-derived suppressor cells(MDSC)in the pathogenesis of this disease by establishing a mouse model of bisphosphonate-related of osteonecrosis of the jaw(BRONJ).Methods:BRONJ-like disease was induced in C57BL/6 mice by intravenous injection of zoledronate to observe gingival healing and alveolar bone repair.In addition,flow cytometry was used to detect the changes in the proportion of MDSC and their subgroups in peripheral blood of BRONJ mice.Results:The extraction cavity of BRONJ mice did not completely heal,showing the empty alveolar fossa.Micro-CT manifested that the extraction socket had scattered high-density images.HE staining showed the absorption of trabecular bone surrounded by multinucleated giant cells.The proportion of MDSC and their subgroups in the peripheral blood of mice was significantly reduced.Conclusions:MDSC differentiation in BRONJ mice model was inhibited which was used to further confirm the mechanism of immune dysfunction in BRONJ.