铁超载通过ASK1-p38通路介导的铁死亡途径抑制成骨细胞功能  

Iron overload downregulates osteoblast function via ASK1-p38 pathway-mediated ferroptosis

作　　者：赵恒伍 王文娟 陈胜武 ZHAO Hengwu;WANG Wenjuan;CHEN Shengwu(Department of Orthopaedics,The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121001,China;Department of Rehabilitation,The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]锦州医科大学附属第三医院骨科,辽宁锦州121001 [2]锦州医科大学附属第一医院康复科,辽宁锦州121001

出　　处：《中国医科大学学报》2021年第6期530-534,共5页Journal of China Medical University

基　　金：辽宁省教育厅科学研究经费项目(JYTQN2020027)。

摘　　要：目的探究不同浓度的枸橼酸铁铵(FAC)对成骨细胞功能的影响及其机制。方法构建人成骨细胞系hFOB1.19细胞培养体系,并用不同浓度(0、100、200μmol/L)的FAC对成骨细胞进行刺激。应用成骨细胞矿化染色测定成骨细胞的成骨功能,应用Western blotting检测骨保护素(OPG)、凋亡信号调节激酶1(ASK1)、p38通路蛋白的表达,应用透射电镜检测成骨细胞铁死亡现象。结果与空白对照组相比,100和200μmol/L FAC刺激显著降低成骨细胞OPG的表达,同时p38、ASK1蛋白磷酸化水平升高。矿化染色结果显示,与空白对照组相比,100和200μmol/L FAC刺激成骨细胞会显著降低成骨细胞的矿化能力。透射电镜结果显示,200μmol/L FAC刺激下成骨细胞出现明显的铁死亡现象。结论FAC能够显著抑制成骨细胞的成骨功能,与ASK1-p38通路的激活有关,并且增强成骨细胞的铁死亡现象。Objective To explore the effects and mechanisms underlying the action of different concentrations of ferric ammonium citrate(FAC)on the function of osteoblasts.Methods A system was created to culture human osteoblast cell line hFOB1.19.Osteoblasts were stimulated with different concentrations of FAC(0,100,and 200μmol/L).Osteoblast mineralization staining was used to determine the osteogenic function.Western blotting was used to detect the expression of osteoprotegerin(OPG),apoptosis signal-regulated kinase 1(ASK1),and p38 pathway proteins.Transmission electron microscopy(TEM)was used to detect ferroptosis in osteoblasts.Results Compared with those in the blank control group,100 and 200μmol/L of FAC significantly decreased the expression of OPG and increased the phosphorylation levels of p38 and ASK1 proteins in osteoblasts.Additionally,in osteoblasts,significantly lesser osteoblast mineralization was observed on using 100 and 200μmol/L of FAC than that in the blank control group.Of note,TEM revealed obvious ferroptosis in osteoblasts stimulated with 200μmol/L of FAC.Conclusion FAC can significantly inhibit the osteogenic function of osteoblasts,which is related to the activation of the ASK1-p38 pathway.Additionally,FAC enhances ferroptosis in osteoblasts.

关 键 词：铁死亡 成骨细胞 凋亡信号调节激酶1-p38 枸橼酸铁铵 

分 类 号：R364.3[医药卫生—病理学]