唑来膦酸对成纤维细胞作用的影响

doi:10.19439/j.sjos.2019.05.008

摘要/Abstract

摘要： 目的分析唑来膦酸对成纤维细胞的影响,探讨唑来膦酸对软组织损伤及引起创口软组织愈合困难的可能机制。方法体外常规培养NIH 3T3成纤维细胞。流式细胞凋亡实验检测加入唑来膦酸后成纤维细胞凋亡的变化。MTT法检测加入唑来膦酸条件下成纤维细胞增殖活性的变化,细胞划痕实验观察唑来膦酸对成纤维细胞迁移能力的影响。采用SPSS 17.0软件包对数据进行统计学分析。结果在药物浓度为5~50 μmol/L范围时,随着药物浓度升高,唑来膦酸促进成纤维细胞凋亡,抑制增殖、迁移的作用逐渐增强。结论唑来膦酸能对软组织造成损伤,可引起拔牙创软组织愈合困难。

关键词: 唑来膦酸, 成纤维细胞, 凋亡, 增殖, 迁移

Abstract: PURPOSE: Bisphosphonates are commonly used to treat bone-derived malignant tumors currently. In recent years, with the widespread use of these drugs, reports on the difficulty of wound healing (DWH) increase remarkably. However, the mechanism is still unclear. The soft tissue injury was suspected to cause DWH in many recent reports. This experiment was designed to explore the influence of zoledronic acid on fibroblast, and investigate the possible mechanisms leading to DWH. METHODS: NIH 3T3 fibroblasts were routinely cultured in vitro. The influence of zoledronic acid on apoptosis, proliferation and migration of fibroblast were tested with flow cytometry, MTT and cell migration assay, respectively. The results of each experimental group were compared with the control group using SPSS 17.0 software package. RESULTS: At a concentration of 5~50 μmol/L, zoledronic acid could dose-dependently inhibit the activity of fibroblast proliferation and migration, and up-regulate apoptosis with significant difference (P<0.05). CONCLUSIONS: Zoledronic acid can up-regulate cell apoptosis, inhibit proliferation and migration of fibroblast, suggesting that soft tissue impairment might contribute to the occurrence of DWH.

Key words: Zoledronic acid, Fibroblast, Apoptosis, Proliferation, Migration

中图分类号:

R739.8

郎淼杰, 区跃坚. 唑来膦酸对成纤维细胞作用的影响[J]. 上海口腔医学, 2019, 28(5): 490-493.

LANG Miao-jie, OU Yue-jian. The influence of zoledronic acid on proliferation, migration and apoptosis of fibroblasts[J]. Shanghai Journal of Stomatology, 2019, 28(5): 490-493.

参考文献

[1] 杨便红. 多发性骨髓瘤使用双瞵酸盐引起颌骨坏死的探讨与护理[J]. 中华现代护理杂志, 2009, 15(15): 1449-1450.
[2] 杨万群, 黄飚, 梁长虹. 双瞵酸盐相关性颌骨坏死影像学研究进展[J]. 中国医学影像技术, 2010, 26(2): 381-383.
[3] Honda Y, Takahashi S, Zhang Y, et al.Effects of bisphosphonate zoledronic acid in hepatocellular carcinoma, depending on mevalonate pathway[J]. J Gastroenterol Hepatol, 2015, 30(3): 619-627.
[4] Luckman SP, Hughes DE, Coxon FP, et al.Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras[J]. J Bone Miner Res, 1998, 13(4):581-589.
[5] Adepitan AO, Ariel B, Lauren L, et al.Osteonecrosis of the jaw in patients treated with denosumab for metastatic tumors to the bone: A series of thirteen patients[J]. J Craniomaxillofac Surg, 2016, 44(3): 265-270.
[6] Kuroshima S, Go VA, Yamashita J.Increased numbers of nonattached osteoclasts after long-term zoledronic acid therapy in mice[J]. Endocrinology, 2012, 153(1): 17-28.
[7] Brown JP, Morin S, Leslie W, et al.Bisphosphonates for treatment of osteoporosis: Expected benefits, potential harms, and drug holidays[J]. Can Fam Physician, 2014, 60(4): 324-333.
[8] Walter C, Pabst A, Ziebart T, et al.Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro[J]. Oral Dis, 2011, 17(2): 194-199.
[9] Vigorita VJ, Silver JS, Eisemon EO.Osteoclast abnormalities in fractured bone during bisphosphonate treatment for osteoporosis: a case report[J]. Skeletal Radiol, 2012, 41(7):861-865.
[10] 李公超. Ⅰ:帕米瞵酸钠对成骨不全成骨细胞和成纤维细胞增殖分化的研究Ⅱ成骨不全成纤维细胞永生化细胞系的建立[D]. 济南: 济南大学, 2011.
[11 Goodwin JS, Zhou J, Kuo YF, et al. Risk of jaw osteonecrosis after intravenous bisphosphonates in cancer patients and patients without cancer[J]. Mayo Clin Proc, 2017, 92(1): 106-113.
[12] Koth VS, Figueiredo MA, Salum FG, et al.Interrelationship of clinical, radiographic and haematological features in patients under bisphosphonate therapy[J]. Dentomaxillofac Radiol, 2017, 46(4): 20160260.
[13] Bagan JV, Jimenez Y, Murillo J, et al.Jaw osteonecrosis associated with bisphosphonates: multiple exposed areas and its relationship to teeth extractions: study of 20 cases[J]. Oral Oncol, 2006, 42(3): 327-329.
[14] Hasegawa T, Kawakita A, Ueda N, et al.A multicenter retrospective study of the risk factors associated with medication-related osteonecrosis of the jaw after tooth extraction in patients receiving oral bisphosphonate therapy: can primary wound closure and a drug holiday really prevent MRONJ?[J]. Osteoporos Int, 2017, 28(8): 2465-2473.
[15] 韩秀丽, 庞雪晶, 兰柳萍, 等. 重组牛碱性成纤维细胞生长因子对腭裂整复术创口愈合的疗效观察[J]. 广东牙病防治, 2014, 22(10): 519-521.

[1]	李欣然, 陈霖, 孟箭. 斑蝥酸钠对人舌鳞癌CAL27细胞的抑制作用及机制研究[J]. 上海口腔医学, 2024, 33(3): 229-234.
[2]	赵炅, 白果, 杨驰. 口腔黏膜成纤维细胞的单细胞转录组特征[J]. 上海口腔医学, 2024, 33(1): 1-5.
[3]	沈忆芬, 刘超, 汤颖, 杨涛, 顾永春. ROS/JNK/caspase 3信号轴在薄荷味电子烟烟液诱导牙周膜干细胞凋亡中的作用[J]. 上海口腔医学, 2024, 33(1): 40-48.
[4]	刘文静, 李梦琦, 崔祥, 汪俊兰. circ_0000326靶向miR-567对口腔鳞状细胞癌HSC3细胞增殖、侵袭及迁移的调控效应[J]. 上海口腔医学, 2023, 32(6): 590-596.
[5]	刘芸, 陈浩月, 米静, 王菲菲, 万光勇, 崔超. 芍药苷对舌鳞癌CAL27细胞的抑制作用及机制探讨[J]. 上海口腔医学, 2023, 32(6): 597-602.
[6]	李胜男, 崔飞艳, 赵姗, 杜琛, 孟箭. 柯里拉京体内外诱导口腔鳞癌CAL-27细胞凋亡及机制探讨[J]. 上海口腔医学, 2023, 32(5): 462-467.
[7]	刘岩, 单丹妮, 孙晶, 邹雨希, 袁长永. Let-7a对人牙髓干细胞增殖、凋亡和成骨分化的影响[J]. 上海口腔医学, 2023, 32(5): 468-474.
[8]	周子超, 束蓉, 吴轶群. EPA对P.gingivalis LPS诱导人牙周膜成纤维细胞炎症反应的影响[J]. 上海口腔医学, 2023, 32(5): 475-479.
[9]	迪丽达尔·塔西甫拉提, 牛雅琪, 热依沙·阿布都克依木, 王玲. 长链非编码RNA AWPPH通过调控Notch信号通路对人牙周膜细胞增殖和成骨向分化的影响[J]. 上海口腔医学, 2023, 32(1): 23-27.
[10]	魏军水, 孙鑫, 徐金标, 陈逸达. LncRNA RUNX1-IT1对恶性多形性腺瘤miR-195/CyclinD1的调控作用探讨[J]. 上海口腔医学, 2023, 32(1): 85-90.
[11]	杨恩黎, 王娜, 李名扬, 李易铭, 耿一鸣, 张东升, 吴海威. 紫草素对血管瘤内皮细胞增殖、凋亡、迁移及成血管的影响[J]. 上海口腔医学, 2022, 31(6): 576-580.
[12]	纳飞, 周建忠, 何永文, 谢志刚, 王荃, 李自良. 鹿茸多肽CNT14对口腔黏膜成纤维细胞增殖、迁移的影响[J]. 上海口腔医学, 2022, 31(6): 607-614.
[13]	江润洋, 康非吾. 唑来膦酸对小鼠下颌拔牙创早期修复过程的影响[J]. 上海口腔医学, 2022, 31(4): 349-353.
[14]	袁尉力, 王绪凯. 口服普萘洛尔对增殖期血管瘤患儿尿液bFGF、MMP-2和MMP-9表达水平的影响[J]. 上海口腔医学, 2022, 31(4): 400-405.
[15]	王雪纯, 吴艳棋, 梅鹏, 张博钧, 朱敏. 低强度牵张应力对异丙肾上腺素诱导下牙周膜成纤维细胞炎症反应的影响[J]. 上海口腔医学, 2022, 31(3): 225-231.