环状RNA PRKCH通过微小RNA-142-3p/肿瘤坏死因子受体相关因子6轴调控炎症刺激软骨细胞生物学特征  

Circ-PRKCH regulates the biological characteristics of chondrocytes stimulated by inflammation via microRNA-142-3p/tumor necrosis factor receptor associated factor 6 axis

作　　者：范忠诚[1] 王琮仁[1] 符策岗 陈晓峰 Fan Zhongcheng;Wang Congren;Fu Cegang;Chen Xiaofeng(Department of Orthopaedics,Haikou Hospital Affiliated to Xiangya School of Medicine,Central South University,Haikou 570208,China;Department of Orthopaedics,Haikou Orthopaedic and Diabetes Hospital,Haikou 570300,China)

机构地区：[1]中南大学湘雅医学院附属海口医院骨科中心,海口570208 [2]海口市骨科与糖尿病医院骨科中心,海口570300

出　　处：《中华实验外科杂志》2023年第8期1566-1569,共4页Chinese Journal of Experimental Surgery

基　　金：海南省卫健委课题(19A200123、20A200518);海南省科技专项资助(ZDYF2020122)。

摘　　要：目的探究环状RNA(circRNA)-PRKCH通过微小RNA(miRNA, miR)-142-3p/肿瘤坏死因子受体相关因子6(TRAF6)轴调控炎症刺激软骨细胞生物学特征的作用及分子机制。方法比较30例骨关节炎患者与30例正常人外周血血清中circ-PRKCH的表达差异, 并在ATDC5细胞中探究circ-PRKCH对细胞增殖、凋亡以及炎性因子分泌等生物学特性的影响。预测并验证circ-PRKCH的下游miRNA、靶基因以及分子间的调控关系。两组间比较应用Student’st检验。结果 circ-PRKCH在骨关节炎患者外周血血清中的表达水平(7.130±1.489)显著高于正常人(2.354±0.982, t=14.670, P<0.01), 并且在脂多糖(LPS)刺激的ATDC5细胞中, circ-PRKCH的表达水平升高(7.890±0.354比1.000±0.757, t=-14.289, P<0.01)。干扰circ-PRKCH同时抑制miR-142-3p或过表达TRAF6可恢复炎症对ATDC5细胞增殖活性的抑制作用(1.541±0.050比0.571±0.051, t=27.161, P<0.01;1.541±0.050比0.555±0.043, t=30.015, P<0.01)、对细胞凋亡的诱导作用(3.963±0.305比15.557±1.146, t=-16.927, P<0.01;3.963±0.305比15.257±0.370, t=-40.763, P<0.01)、对肿瘤坏死因子-α(TNF-α)分泌的促进作用(297.464±17.862比591.626±40.527, t=-11.504, P<0.01;297.464±17.862比594.953±20.252, t=-19.081, P<0.01)以及对白细胞介素-8(IL-8)分泌的促进作用(234.309±11.755比661.416±33.197, t=-21.006, P<0.01;234.309±11.755比658.751±21.369, t=-30.143, P<0.01)。结论 circ-PRKCH可通过miR-142-3p/TRAF6轴调控炎症刺激软骨细胞的生物学特征。Objective To investigate the role and mechanism of circular RNA(circRNA)-PRKCH in regulating the biological characteristics of inflammation-stimulated chondrocytes via the micro RNA(miRNA,miR)-142-3p/tumor necrosis factor receptor associated factor 6(TRAF6)axis.Methods The differences of circ-PRKCH expression in peripheral blood serum of 30 patients with osteoarthritis and 30 normal subjects were compared,and the effects of circ-PRKCH on the biological properties including cell proliferation,apoptosis and inflammatory factors secretion in ATDC5 cells.The downstream miRNAs,target genes and regulatory relationships of circ-PRKCH were predicted and validated.Student’s t-test was applied to two sets of measures that met normal distribution.Results Circ-PRKCH expression levels were significantly higher in peripheral blood serum of patients with osteoarthritis(7.130±1.489)than in normal subjects(2.354±0.982,t=14.670,P<0.01)and were elevated in lipopolysaccharide(LPS)-stimulated ATDC5 cells(7.890±0.354 vs.1.000±0.757,t=-14.289,P<0.01).Interfering with circ-PRKCH while inhibiting miR-142-3p or overexpressing TRAF6 restored the inhibitory effect of inflammation on the cell proliferative activity(1.541±0.050 vs.0.571±0.051,t=27.161,P<0.01;1.541±0.050 vs.0.555±0.043,t=30.015,P<0.01),induction of cell apoptosis(3.963±0.305 vs.15.557±1.146,t=-16.927,P<0.01;3.963±0.305 vs.15.257±0.370,t=-40.763,P<0.01),promotion of tumor necrosis factor-α(TNF-α)secretion(297.464±17.862 vs.591.626±40.527,t=-11.504,P<0.01;297.464±17.862 vs.594.953±20.252,t=-19.081,P<0.01)and interleukin-8(IL-8)secretion(234.309±11.755 vs.661.416±33.197,t=-21.006,P<0.01;234.309±11.755 vs.658.751±21.369,t=-30.143,P<0.01)in ATDC5.Conclusion Circ-PRKCH can regulate the biological characteristics of inflammation-stimulated chondrocytes through the miR-142-3p/TRAF6 axis.

关 键 词：骨关节炎 外泌体 环状RNA PRKCH 微小RNA-142-3p 肿瘤坏死因子受体相关因子6 

分 类 号：R684.3[医药卫生—骨科学]