椎间盘退变IL-1β激活NF-κB信号通路增强ADAMTS-4的表达  

IL-1β activates the NF-κB signal pathway to enhance the expression of ADAMTS-4 in intervertebral disc degeneration

作　　者：李瑶[1] 孙中仪 戴健[3] 蒋海涛 张铖 唐晓明[3] LI Yao;SUN Zhong-yi;DAI Jian;JIANG Hai-tao;ZHANG Cheng;TANG Xiao-ming(Nanjing Medical University,Nanjing 211100,China;Department of Orthopedics,Nanjing Jiangbei People's Hospital,Nanjing 211500,China;Department of Orthopedics,The First Hospital of Huaian City,Nanjing Medical University,Huaian 223300,China)

机构地区：[1]南京医科大学,江苏南京211100 [2]南京江北医院骨科,江苏南京211500 [3]南京医科大学附属淮安第一医院骨科,江苏淮安223300

出　　处：《中国矫形外科杂志》2021年第23期2177-2181,共5页Orthopedic Journal of China

基　　金：南京医科大学附属淮安第一医院高层次人才课题项目(编号:YGRX201904);南京江北医院省级科研培育项目(编号:JKK201902)。

摘　　要：[目的]比较未退变与退变髓核细胞基质标志物的表达,并探讨IL-1β通过NF-κB信号通路对ADAMTS-4表达的调控作用。[方法]收集退变人类椎间盘组织,分离培养人髓核细胞。采用qRT-PCR和Western blot检测基质标志物表达。对退变髓核细胞给予IL-1β和NF-κB通路抑制剂BAY11-7082处理,检测ADAMTS-4和其它标志物的表达。[结果]随着IL-1β浓度的升高,未退变髓核细胞的活性逐渐减低,呈剂量依赖。与未退变髓核细胞相比,退变髄核细胞的ADAMTS-4和IL-1β的表达显著升高(P<0.05),而Agg和ColⅡ的表达显著降低(P<0.05)。对退变髓核细胞进行处理,与空白对照相比,IL-1β可显著增加退变髓核细胞ADAMTS-4的mRNA表达,而降低Agg和ColⅡ的表达(P<0.05),而BAY11-7082可非常显著的逆转IL-1β的作用,显著降低ADAMTS-4的表达,而增加Agg和ColⅡ表达(P<0.05)。[结论]IL-1β可通过调节NF-κB信号的活性来增加ADAMTS-4在髓核细胞中的表达,降低Agg和ColⅡ的表达。[Objective]To compare the expression of matrix markers in non-degenerated and degenerated nucleus pulposus cells,and to explore the effect of IL-1βon the expression of ADAMTS-4 through the NF-κB signaling pathway.[Methods]Human nucleus pulposus cells were isolated and cultured from the tissue harvested from discectomy in clinical practice.The expressions of matrix markers and related materials were detected by qRT-PCR and Western blot.In addition,the expression of ADAMTS-4 and other markers in the supernatant were assayed after the degenerated nucleus pulposus cells were treated with IL-1βand NF-κB pathway inhibitor-BAY 11-7082.[Results]With the increase of IL-1βconcentration,the activity of non-degenerated nucleus pulposus cells gradually decreased in a dose-dependent manner.Compared with non-degenerated nucleus pulposus cells,the expressions of ADAMTS-4 and IL-1βin degenerated nucleus pulposus cells were significantly increased(P<0.05),while the expressions of Agg and ColⅡwere significantly decreased(P<0.05).In term of treatments in vitro,IL-1βsignificantly increased the expression of ADAMTS-4 in degenerated nucleus pulposus cells,while reducing the expression of Agg and ColⅡcompared with the blank control(P<0.05),whereas the BAY11-7082 significantly reversed the effect of IL-1β,which significantly reduced the expression of ADAMTS-4,and increased the expression of Agg and Col II(P<0.05).[Conclusion]The IL-1βdoes increase the expression of ADAMTS-4 in nucleus pulposus cells,while decrease the expression of Agg and ColⅡ,which might be regulated through the NF-κB signal pathway.

关 键 词：椎间盘退变 髓核细胞 IL-1Β ADAMTS-4 NF-ΚB 

分 类 号：R738.1[医药卫生—肿瘤]