[1]梁小弟,梁小菊,李芙蓉,等.生长分化因子-15在白细胞介素-1β诱导软骨细胞凋亡与炎症中的作用及潜在机制[J].陕西医学杂志,2021,50(3):280-284.[doi:DOI:10.3969/j.issn.1000-7377.2021.03.006]
　LIANG Xiaodi,LIANG Xiaoju,LI Furong,et al.Role and potential mechanism of GDF-15 in apoptosis and inflammation of chondrocytes induced by IL-1β[J].,2021,50(3):280-284.[doi:DOI:10.3969/j.issn.1000-7377.2021.03.006]
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生长分化因子-15在白细胞介素-1β诱导软骨细胞凋亡与炎症中的作用及潜在机制
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
50
期数:
2021年3期
页码:
280-284
栏目:
基础研究
出版日期:
2021-03-01

文章信息/Info

Title:
Role and potential mechanism of GDF-15 in apoptosis and inflammation of chondrocytes induced by IL-1β
作者:
梁小弟1; 梁小菊2; 李芙蓉3; 石茂才1
(1.定西市人民医院骨科,甘肃 定西 743000; 2.西安交通大学附属红会医院小儿骨科,陕西 西安 710054; 3.定西市人民医院麻醉科,甘肃 定西 743000)
Author(s):
LIANG Xiaodi; LIANG Xiaoju; LI Furong; SHI Maocai
(Department of Orthopedics,Dingxi People's Hospital,Dingxi 743000,China)
关键词:
骨性关节炎;  软骨细胞;  生长分化因子-15;  细胞凋亡;  炎症;  白细胞介素-1β
Keywords:
Osteoarthritis;  Chondrocyte;  GDF-15;  Apoptosis;  Inflammation;  IL-1β
分类号:
R 684.3
DOI:
DOI:10.3969/j.issn.1000-7377.2021.03.006
文献标志码:
A
摘要:
目的:探讨生长分化因子-15(GDF-15)在白细胞介素-1β(IL-1β)诱导的软骨细胞凋亡与炎症中的作用及潜在机制。方法:不同浓度IL-1β(1、5、10、15 ng/ml)处理正常人膝关节软骨细胞(NHAC-kn)24 h以模拟骨性关节炎(OA)的细胞模型。CCK-8实验检测不同浓度IL-1β处理后的NHAC-kn细胞活性。将GDF-15过表达质粒和空载体质粒分别转染到NHAC-kn细胞中,24 h后收集转染细胞,采用定量逆转录-聚合酶链反应(RT-PCR)检测GDF-15 mRNA水平,采用Western blot检测一氧化氮合酶(iNOS)、环氧化酶2(COX-2)、磷酸化蛋白激酶B(p-AKT)、蛋白激酶B(AKT)、p-p65和p65蛋白水平,采用ELISA实验检测上清液中半胱氨酸-天冬氨酸蛋白酶-3(Caspase-3)、一氧化氮(NO)、前列腺素E2(PGE2)、白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量,采用流式细胞术检测细胞凋亡率。结果:GDF-15表达量在IL-1β处理的软骨细胞中显著下调(P<0.05)。过表达GDF-15抑制IL-1β诱导的软骨细胞凋亡和Caspase-3活性,显著下调IL-1β诱导的软骨细胞NO和PGE2水平以及iNOS和COX-2蛋白表达水平,显著减少IL-1β诱导的IL-6和TNF-α水平(均P<0.05)。GDF-15激活PI3K/AKT/NF-κB信号通路。抑制PI3K/AKT/NF-κB通路部分逆转了GDF-15对IL-1β诱导的软骨细胞凋亡和炎症的缓解作用。结论:GDF-15可能通过激活PI3K/AKT/NF-κB通路抑制IL-1β诱导的软骨细胞凋亡和炎症反应。
Abstract:
Objective:To investigate the role and potential mechanism of GDF-15 in apoptosis and inflammation of chondrocytes induced by IL-1β.Methods:Different concentrations of IL-1β(1,5,10,15 ng/ml)were treated with NHAC-kn for 24 hours to simulate the cell model of osteoarthritis(OA).CCK-8 experiment was used to detect the activity of NHAC-kn cells treated with different concentrations of IL-1β.The GDF-15 overexpression plasmid and the empty vector plasmid were transfected into NHAC-kn cells respectively.The transfected cells were collected 24 hours later,and the GDF-15 mRNA level was detected by RT-PCR,and Western blot was used to detect iNOS,COX-2,p-AKT,AKT,p-p65 and p65 protein levels,and ELISA was used to detect Caspase-3,NO,PGE2,IL-6 and TNF-α content,and flow cytometry was used to detect cell apoptosis rate.Results:GDF-15 expression was significantly down-regulated in IL-1β-treated chondrocytes(P<0.05).Overexpression of GDF-15 inhibited IL-1β-induced chondrocyte apoptosis and Caspase-3 activity,and significantly reduced the levels of NO,PGE2,iNOS,COX-2,IL-6 and TNF-α induced by IL-1β(all P<0.05).GDF-15 could activate the PI3K/AKT/NF-κB pathway,and inhibition of PI3K/AKT/NF-κB pathway partially reversed the alleviating effect of overexpression of GDF-15 on IL-1β-induced chondrocyte damage.Conclusion:GDF-15 activates the PI3K/AKT/NF-κB pathway and inhibits IL-1β-induced chondrocyte apoptosis and inflammation.

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备注/Memo

备注/Memo:
基金项目:甘肃省定西市自然科学基金资助项目(DX2020Z01-4)
更新日期/Last Update: 2021-03-04