FGF18通过上调BMP2诱导人牙龈成纤维细胞向成骨样细胞分化  

FGF18 induces differentiation of human gingival fibroblasts into osteoblasts by upregulating BMP2

作　　者：侯亚丽[1] 刘慧娟 张昊[3] 孙婧媛 宋鹏[1] 刘月瑶 李荷香[1] Hou Yali;Liu Huijuan;Zhang Hao;Sun Jingyuan;Song Peng;Liu Yueyao;Li Hexiang(Dept of Pathology,Hebei Medical University,Shijiazhuang 050017;Hebei Key Laboratory of Stomatology,Hebei Technology Innovation Center of Oral Health,Shijiazhuang 050017;Dept of Oral and Maxillofacial Surgery,School and Hospital of Stomatology,Hebei Medical University,Shijiazhuang 050017)

机构地区：[1]河北医科大学口腔医院病理科,石家庄050017 [2]河北省口腔医学重点实验室,河北省口腔健康技术创新中心,石家庄050017 [3]河北医科大学口腔医院口腔颌面外科,石家庄050017

出　　处：《安徽医科大学学报》2025年第2期279-285,共7页Acta Universitatis Medicinalis Anhui

基　　金：河北省2019年度医学科学研究课题(编号:20191076);河北医科大学2023年大学生创新性实验计划项目(编号:USIP2023235)。

摘　　要：目的研究成纤维细胞生长因子18(FGF18)是否能诱导体外分离培养的人牙龈成纤维细胞(HGFs)向成骨样细胞分化,并探究其成骨机制。方法组织块法分离培养HGFs并鉴定。取第3代HGFs,分为实验组和对照组。实验组加入FGF18和L-DMEM、对照组加入L-DMEM。噻唑蓝(MTT)法检测不同浓度FGF18(0、0.01、0.02、0.04、0.06 mg/L)对HGFs增殖影响;碱性磷酸酶(ALP)和茜素红染色检测成骨能力和矿化能力;RT-PCR、免疫细胞化学染色及Western blot检测成骨相关基因、蛋白和BMP信号通路中BMP2基因和蛋白表达情况。结果与对照组比较,实验组培养3、5、7、9、11 d均可促进HGFs增殖(P<0.05);培养14、21 d ALP活性、矿物盐沉积均增高(P<0.05),ALP、OPN、OCN及BMP信号通路中BMP2 mRNA表达均明显增高(P<0.01)。培养21 d OPN、OCN及BMP2蛋白表达较培养14 d明显增高(P<0.01)。结论FGF18能促进HGFs增殖,诱导HGFs向功能性成骨样细胞分化,其成骨机制与上调BMP2有关。Objective To investigate whether fibroblast growth factor 18(FGF18)can induce human gingival fibroblasts(HGFs)isolated in vitro to differentiate into osteoblast-like cells,and to explore the mechanism of osteogenesis.Methods HGFs were isolated,cultured and identified by tissue block method.The third generation of HGFs were divided into experimental group and control group.FGF18 and L-DMEM was added to the experimental group while L-DMEM was added to the control group.The effects of different concentrations of FGF18(0,0.01,0.02,0.04,0.06 mg/L)on proliferation of HGFs were detected by Methylthiazolyldiphenyl-tetrazolium bromide(MTT)assay.Alkaline phosphatase(ALP)and alizarin red staining were used to detect the osteogenesis and mineralization ability of the cells after induction.RT-PCR,immunocytochemistry staining,and Western blot were used to detect the expression of genes and proteins related to osteogenesis and BMP2 in the BMP signaling pathway.Results Compared with the control group,the experimental group could promote the proliferation of HGFs at 3,5,7,9,and 11days(P<0.05),ALP activity and mineral salt deposition increased after induction at 14 and 21 days(P<0.05),and the expressions of ALP,OPN,OCN mRNA and BMP2 mRNA in BMP signaling pathway significantly increased(P<0.01).The expressions of OPN,OCN and BMP2 protein at 21 days were significantly higher than those at 14 days(P<0.01).Conclusion FGF18 can promote the proliferation of HGFs,and induce the differentiation of HGFs into functional osteoblasts.The osteogenic mechanism is related to the upregulation of BMP2.

关 键 词：人牙龈成纤维细胞 FGF18 成骨 诱导 细胞分化 增殖 

分 类 号：R780.2[医药卫生—口腔医学]