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、200 μmol/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200 μmol/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200 μmol/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，200 μmol/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。

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

赵恒伍¹, 王文娟², 陈胜武¹

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

收稿日期:2020-11-07出版日期:2021-06-30发布日期:2021-05-28
通讯作者:陈胜武E-mail:csw020913@sina.com
作者简介:赵恒伍(1985-),男,主治医师,硕士.
基金资助:辽宁省教育厅科学研究经费项目（JYTQN2020027）


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
Abstract: 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 200 μmol/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 200 μmol/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 200 μmol/L of FAC than that in the blank control group. Of note,TEM revealed obvious ferroptosis in osteoblasts stimulated with 200 μmol/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.
Key words: ferroptosis, osteoblast, apoptosis signal-regulated kinase 1-p38, ferric ammonium citrate
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