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

›› 2020, Vol. 11 ›› Issue (1): 41-44.

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

田美¹,魏斌²,王丹妮¹,孙国文³

1. 南京大学医学院附属口腔医院，南京市口腔医院
2. 南京市江宁医院，南京医科大学附属江宁医院
3. 南京市口腔医院口腔颌面外科

收稿日期:2019-11-25 修回日期:2020-02-18 出版日期:2020-03-25 发布日期:2020-04-07
通讯作者: 孙国文 E-mail:238957@sina.com

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

Received:2019-11-25 Revised:2020-02-18 Online:2020-03-25 Published:2020-04-07

摘要/Abstract

摘要： 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分析小鼠外周血中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。

关键词: 双膦酸盐性颌骨坏死, 髓系抑制细胞, 单核细胞

Abstract: 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.

Key words: Bisphosphonate-related osteonecrosis of the jaws, Myeloid-derived suppressor cell, monocytes

中图分类号:

R782

田美魏斌王丹妮孙国文. 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[J]. 口腔生物医学, 2020, 11(1): 41-44.

参考文献 18

[1]	Ruggiero SL, Dodson TB, Fantasia J, et al.American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update[J].J Oral Maxillofac Surg, 2014, 72(10):1938-1956
[2]	Shapiro CL, Van Poznak C, Lacchetti C, et al.Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO Clinical Practice Guideline[J].J Clin Oncol, 2019, 37(31):2916-2946
[3]	Kim ND, Luster AD.The role of tissue resident cells in neutrophil recruitment[J].Trends Immunol, 2015, 36(9):547-555
[4]	Soumelis V, Pattarini L, Michea P, et al.Systems approaches to unravel innate immune cell diversity, environmental plasticity and functional specialization[J].Curr Opin Immunol, 2015, 32:42-47
[5]	Kolaczkowska E, Kubes P.Neutrophil recruitment and function in health and inflammation[J].Nat Rev Immunol, 2013, 13(3):159-175
[6]	Patntirapong S, Poolgesorn M.Alteration of macrophage viability,differentiation,and function by bisphosphonates[J].Oral Dis, 2018, 24(7):1294-1302
[7]	Hagelauer N, Pabst AM, Ziebart T, et al.In vitro effects of bisphosphonates on chemotaxis, phagocytosis, and oxidative burst of neutrophil granulocytes[J].Clin Oral Investig, 2015, 19(1):139-148
[8]	Kozicky LK, Sly LM.Depletion and Reconstitution of Macrophages in Mice[J].Methods Mol Biol, 2019, 1960:101-112
[9]	Gabrilovich DI.Myeloid-Derived Suppressor Cells[J].Cancer Immunol Res, 2017, 5(1):3-8
[10]	Zhang H, Maric I, Diprima MJ, et al.Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer[J].Blood, 2013, 122(7):1105-1113
[11]	Kuroshima S, Sasaki M, Sawase T.Medication-related osteonecrosis of the jaw: A literature review[J].J Oral Biosci, 2019, 61(2):99-104
[12]	Endo Y, Kumamoto H, Nakamura M, et al.Underlying Mechanisms and Therapeutic Strategies for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)[J].Biol Pharm Bull, 2017, 40(6):739-750
[13]	Greten TF, Manns M P, Korangy F.Myeloid derived suppressor cells in human diseases[J].Int Immunopharmacol, 2011, 11(7):802-807
[14]	Zhang Q, Atsuta I, Liu S, et al.IL-17-mediated M1M2 macrophage alteration contributes to pathogenesis of bisphosphonate-related osteonecrosis of the jaws[J].Clin Cancer Res, 2013, 19(12):3176-3188
[15]	Kuiper JW, Forster C, Sun C, et al.Zoledronate and pamidronate depress neutrophil functions and survival in mice[J].Br J Pharmacol, 2012, 165(2):532-539
[16]	Kikuiri T, Kim I, Yamaza T, et al.Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice[J].J Bone Miner Res, 2010, 25(7):1668-1679
[17]	Poe SL, Arora M, Oriss TB, et al.STAT1-regulated lung MDSC-like cells produce IL-10 and efferocytose apoptotic neutrophils with relevance in resolution of bacterial pneumonia[J].Mucosal Immunol, 2013, 6(1):189-199
[18]	Ren D, Bi Q, Li L, et al.Myeloid-derived suppressor cells accumulate in the liver site after sepsis to induce immunosuppression[J].Cell Immunol, 2012, 279(1):12-20