网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
circDHRS3通过调节TLR4/NF-κB信号通路对关节软骨细胞增殖和凋亡的影响
作者:李俊  陈建生  周文彬 
单位:苏州市中西医结合医院 骨科, 江苏 苏州 215100
关键词:circDHRS3 TLR4/NF-κB信号通路 关节软骨细胞 增殖 凋亡 
分类号:R684
出版年·卷·期(页码):2022·50·第八期(934-939)
摘要:

目的:探讨circDHRS3通过调节TLR4/NF-κB信号通路对关节软骨细胞增殖和凋亡的影响。方法:体外分离培养人关节软骨细胞,用不同浓度(0、1、5、10 μg·L-1)的IL-1β处理,采用qRT-PCR检测circDHRS3的表达。选取10 μg·L-1处理关节软骨细胞,将细胞分组,分别为Control组、IL-1β组、IL-1β+si-NC组、IL-1β+si-circDHRS3组、IL-1β+si-circDHRS3+pcDNA组和IL-1β+si-circDHRS3+TLR4组。CCK8检测细胞活力,流式细胞术检测细胞凋亡;Weatern blot检测p21、PCNA、Bcl-2、Bax和TLR4/NF-κB信号通路相关蛋白的表达。结果:经过不同浓度IL-1β处理关节软骨细胞后,circDHRS3在软骨细胞中高表达,呈浓度依赖性。与Control组相比,IL-1β组抑制细胞活力及PCNA、Bcl-2蛋白表达,促进细胞凋亡及p21、Bax、TLR4和p-NF-κB蛋白表达;与IL-1β+si-NC组相比,IL-1β+si-circDHRS3组促进细胞活力及PCNA、Bcl-2蛋白表达,抑制细胞凋亡及p21、Bax、TLR4和p-NF-κB蛋白表达;与IL-1β+si-circDHRS3+pcDNA组相比,IL-1β+si-circDHRS3+TLR4组抑制细胞活力及PCNA、Bcl-2蛋白表达,促进细胞凋亡及p21、Bax蛋白表达。结论:circDHRS3通过上调TLR4/NF-κB信号通路抑制关节软骨细胞的增殖和诱导细胞的凋亡。

Objective: To investigate the effect of circDHRS3 on the proliferation and apoptosis of articular chondrocytes by regulating the TLR4/NF-κB signaling pathway.Methods: Human articular chondrocytes were isolated and cultured in vitro,treated with IL-1β at different concentrations (0,1,5,10 μg·L-1),and the expression of circDHRS3 was detected by qRT-PCR.Select 10 μg·L-1 to treat articular chondrocytes,and divide the cells into control group,IL-1β group,IL-1β+si-NC group,IL-1β+si-circDHRS3 group,IL-1β+si-circDHRS3+pcDNA group and IL-1β+si-circDHRS3+TLR4 group.Cell viability was detected using CCK8;cell apoptosis was detected with flow cytometry;Weatern blot was used to detect the expression of p21,PCNA,Bcl-2,Bax and TLR4/NF-κB signaling pathway related proteins.Results: After treating articular chondrocytes with different concentrations of IL-1β,circDHRS3 was highly expressed in chondrocytes in a concentration-dependent manner.Compared with the control group,the IL-1β group inhibited cell viability,PCNA,Bcl-2 protein expression;and promoted the rate of cell apoptosis,p21,Bax,TLR4 and p-NF-κB protein expression.Compared with IL-1β+si-NC group,IL-1β+si-circDHRS3 group promoted cell viability,PCNA,Bcl-2 protein expression;inhibited cell apoptosis rate,p21,Bax,TLR4 and p-NF-κB protein expression.Compared with IL-1β+si-circDHRS3+pcDNA group,IL-1β+si-circDHRS3+TLR4 group inhibited cell viability,PCNA,Bcl-2 protein expression;promoted cell apoptosis rate,p21 protein expression,and Bax protein expression significantly elevated.Conclusion: circDHRS3 inhibits the proliferation of articular chondrocytes and induces cell apoptosis by up-regulating the TLR4/NF-κB signaling pathway.

参考文献:

[1] VINA E R,KWOH C K.Epidemiology of osteoarthritis:literature update[J].Curr Opin Rheumatol,2018,30(2):160-167.
[2] 胥少汀,葛宝丰,徐印坎.实用骨科学[M].3版.北京:人民军医出版社,2005.
[3] ABRAMOFF B,CALDERA F E.Osteoarthritis:pathology,diagnosis,and treatment options[J].Med Clin North Am,2020,104(2):293-311.
[4] WANG Y,WU C Y,ZHANG Y N,et al.Screening for differentially expressed circRNA between Kashin-Beck disease and osteoarthritis patients based on circRNA chips[J].Clin Chim Acta,2020,501:92-101.
[5] WANG Y,WU C Y,ZHANG F,et al.Screening for differentially expressed circular RNAs in the cartilage of osteoarthritis patients for their diagnostic value[J].Genet Test Mol Biomarkers,2019,23(10):706-716.
[6] JIANG R,GAO H,CONG F,et al.Circ_DHRS3 positively regulates GREM1 expression by competitively targeting miR-183-5p to modulate IL-1β-administered chondrocyte proliferation,apoptosis and ECM degradation[J].Int Immunopharmacol,2020,91:107293.
[7] 王永福,林剑,詹宏刚.CD14/TLR-4-NF-κB信号通路参与骨关节炎发病机制的研究[J].实用骨科杂志,2013,19(6):528-530.
[8] 林道冠,徐桂丽.基于miRNA-30b-5p/TLR4/NF-κB轴探究针灸改善大鼠膝骨关节炎损伤的实验研究[J].中国免疫学杂志,2019,35(22):2730-2735.
[9] 徐雪妮,潘玉琴.环状RNA的功能及其与结直肠癌发生、发展关系的研究进展[J].东南大学学报(医学版),2019,38(3):527-531.
[10] WU Y G,LU X X,SHEN B,et al.The therapeutic potential and role of miRNA,lncRNA,and circRNA in osteoarthritis[J].Curr Gene Ther,2019,19(4):255-263.
[11] LI H Z,LIN Z,XU X H,et al.The potential roles of circRNAs in osteoarthritis:a coming journey to find a treasure[J].Biosci Rep,2018,38(5):BSR20180542.
[12] ZHOU Z B,HUANG G X,FU Q,et al.circRNA.33186 contributes to the pathogenesis of osteoarthritis by sponging miR-127-5p[J].Mol Ther,2019,27(3):531-541.
[13] SHEN S Y,WU Y Z,CHEN J X,et al.CircSERPINE2 protects against osteoarthritis by targeting miR-1271 and ETS-related gene[J].Ann Rheum Dis,2019,78(6):826-836.
[14] HUANG Z H,MA W M,XIAO J H,et al.CircRNA_0092516 regulates chondrocyte proliferation and apoptosis in osteoarthritis through the miR-337-3p/PTEN axis[J].J Biochem,2020:mvaa119.
[15] WU Q,YUAN Z H,MA X B,et al.Low expression of CircRNA HIPK3 promotes osteoarthritis chondrocyte apoptosis by serving as a sponge of miR-124 to regulate SOX8[J].Eur Rev Med Pharmacol Sci,2020,24(15):7937-7945.
[16] 卓泽铭,范忠诚,郭祥.桑寄生提取物联合miR-375对骨关节炎软骨细胞活力和凋亡的影响[J].中国病理生理杂志,2020,36(6):1082-1088.
[17] 王西彬,左瑞庭.葫芦素B对IL-1β诱导的软骨细胞损伤及胞外基质代谢紊乱的影响[J].天津医药,2019,47(12):1210-1214.
[18] MELIT L E,MǎRGINEAN CO,MǎRGINEAN C D,et al.The relationship between toll-like receptors and helicobacter pylori-related gastropathies:still a controversial topic[J].J Immunol Res,2019,2019:8197048.
[19] DING Y J,WANG L F,ZHAO Q,et al.MicroRNA93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NFκB signaling pathway[J].Int J Mol Med,2019,43(2):779-790.
[20] 俞银贤,陈金伟,阮琪,等.TLR4/NF-κB在国人膝关节OA关节软骨中表达的实验研究[J].生物骨科材料与临床研究,2015,12(4):4-7,81.
[21] 董小君.风湿宁对风寒湿痹证CIA模型TLR4/NF-κB信号通路的作用机制研究[D].成都:成都中医药大学,2018.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 752109 位访问者


 ©《现代医学》编辑部
联系电话:025-83272481;83272479
电子邮件: xdyx@pub.seu.edu.cn

苏ICP备09058541