[1]李义,杨彦君,殷天坪,等.NCOA4调控SLC7A11/GPX4通路对膝骨关节炎大鼠软骨细胞铁死亡的影响实验研究[J].陕西医学杂志,2025,54(6):729-735.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.002]
　LI Yi,YANG Yanjun,YIN Tianping,et al.Effect of NCOA4 on ferroptosis of chondrocytes in rats with knee osteoarthritis by regulating SLC7A11/GPX4 pathway[J].,2025,54(6):729-735.[doi:DOI:10.3969/j.issn.1000-7377.2025.06.002]
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NCOA4调控SLC7A11/GPX4通路对膝骨关节炎大鼠软骨细胞铁死亡的影响实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年6期
页码:
729-735
栏目:
基础研究
出版日期:
2025-06-05

文章信息/Info

Title:
Effect of NCOA4 on ferroptosis of chondrocytes in rats with knee osteoarthritis by regulating SLC7A11/GPX4 pathway
作者:
李义; 杨彦君; 殷天坪; 谢正兴; 唐良华
（贵州中医药大学第二附属医院关节骨科，贵州 贵阳 550001）
Author(s):
LI Yi; YANG Yanjun; YIN Tianping; XIE Zhengxing; TANG Lianghua
(Department of Orthopedics,the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China)
关键词:
骨关节炎; 核受体共激活因子4; 溶质载体家族7成员11; 谷胱甘肽过氧化物酶4; 铁死亡; 软骨
Keywords:
Osteoarthritis; Nuclear receptor coactivator 4; Solute carrier family 7 member 11; Glutathione peroxidase 4; Ferroptosis; Cartilage
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2025.06.002
文献标志码:
A
摘要:
目的：探讨核受体共激活因子4（NCOA4）调控溶质载体家族7成员11（SLC7A11）/谷胱甘肽过氧化物酶4（GPX4）通路对膝骨关节炎大鼠软骨细胞铁死亡的影响。方法：将50只大鼠利用随机数字表法分为Con组（正常对照组）、Model组（膝骨关节炎模型大鼠）、si-NC组（膝骨关节炎模型大鼠，体内转染si-NC阴性对照）、si-NCOA4组（膝骨关节炎模型大鼠，体内转染si-NCOA4）和RSL3组（膝骨关节炎模型大鼠，体内转染si-NCOA4并腹腔注射5 mg/kg铁死亡诱导剂RSL3），每组10只。观察大鼠行为，进行Lequesne MG评分；HE染色和番红O-固绿染色评估关节软骨的病变程度；检测软骨组织的铁含量；蛋白免疫印迹检测NCOA4、铁死亡相关蛋白、SLC7A11和GPX4蛋白表达情况；实时荧光定量PCR（RT-qPCR）检测NCOA4 mRNA表达水平。结果：NCOA4在OA大鼠软骨组织中表达上调（P<0.05）。与Con组比较，Model组和si-NC组Lequesne MG评分、Mankin评分、4-羟壬二酸酯（4HNE）蛋白表达、铁含量、活性氧（ROS）和丙二醛（MDA）水平增加，铁蛋白重链1（FTH1）、闪存转换层（FTL）、溶质载体家族7成员11（SLC7A11）、GPX4蛋白表达及超氧化物歧化酶（SOD）水平降低（均P<0.05）。与Model组和si-NC组比较，si-NCOA4组Lequesne MG评分、Mankin评分、4HNE蛋白表达、铁含量、ROS和MDA水平降低，FTH1、FTL、SLC7A11、GPX4蛋白表达及SOD水平增加（均P<0.05）。与si-NCOA4组比较，RSL3组Lequesne MG评分、Mankin评分、4HNE蛋白表达、铁含量、ROS和MDA水平增加，FTH1、FTL、SLC7A11、GPX4蛋白表达及SOD水平显著降低（均P<0.05）。结论：NCOA4通过抑制与SLC7Al1/GPX4信号通路促进铁蛋白自噬促进铁死亡过程，从而促进OA的发展。
Abstract:
Objective:To investigate the effect of nuclear receptor coactivator 4 (NCOA4) on ferroptosis of chondrocytes in rats with knee osteoarthritis (OA) by regulating solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway.Methods：Fifty rats were randomly divided into Con group (normal control group),Model group (knee osteoarthritis model rats),si-NC group (knee osteoarthritis model rats were transfected with si-NC negative control in vivo),si-NCOA4 group (knee osteoarthritis model rats were transfected with si-NCOA4 in vivo),and RSL3 group (knee osteoarthritis model rats were transfected with si-NCOA4 in vivo and intraperitoneally injected with 5 mg/kg ferroptosis inducer RSL3),with 10 rats in each group.The behavior of rats was observed and Lequesne MG score was performed.HE staining and safranin O-fast green staining were used to evaluate the degree of articular cartilage lesions.The iron concentration within cartilage tissue was assayed.Expression levels of NCOA4,as well as ferroptosis-associated proteins SLC7A11 and GPX4,were detected by Western blot.The relative expression level of NCOA4 mRNA was detected by RT-qPCR.Results:The expression of NCOA4 in cartilage tissue of OA rats was significantly up-regulated (P<0.05).In comparison to the Con group,the Lequesne MG score,Mankin score,expression of 4HNE protein,and levels of iron content,ROS and MDA were notably elevated in both the Model and si-NC groups,and the protein expressions of FTH1,FTL,SLC7A11,GPX4,and SOD level were significantly decreased (all P<0.05).In comparison to the Model group and si-NC group,Lequesne MG score,Mankin score,expression of 4HNE protein,levels of iron content,ROS and MDA in si-NCOA4 group were significantly decreased,while FTH1,FTL,SLC7A11,GPX4 protein expressions and SOD level were significantly increased (all P<0.05).Compared with si-NCOA4 group,Lequesne MG score,Mankin score,4HNE protein expression,levels of iron content,ROS and MDA in RSL3 group were significantly increased,while FTH1,FTL,SLC7A11,GPX4 protein expressions and SOD level were significantly decreased(all P<0.05).Conclusion:NCOA4 promotes the development of OA by inhibiting the SLC7Al1/GPX4 signaling pathway to promote ferritin autophagy and ferroptosis.

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备注/Memo

备注/Memo:
贵州省科技计划项目（黔科合基础-ZK[2023]一般435）；贵州中医药大学骨伤学院学科建设资助项目（骨伤学科资助2024号）
更新日期/Last Update: 2025-06-04