β-catenin与NF-κB信号通路在膝骨关节炎滑膜炎症中的表达特点及意义
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作者Author单位AddressE-Mail
张栋 ZHANG Dong 北京中医药大学, 北京 100029
北京中医药大学东方医院, 北京 100078
 
王庆甫 WANG Qing-fu 北京中医药大学第三附属医院, 北京 100029 The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China qingpu-wang@sohu.com 
张晓哲 ZHANG Xiao-zhe 北京中医药大学, 北京 100029  
阮安民 RUAN An-min 北京中医药大学, 北京 100029  
田宇 TIAN Yu 北京中医药大学, 北京 100029  
刘思婷 LIU Si-ting 北京中医药大学, 北京 100029  
樊小燕 FAN Xiao-yan 北京中医药大学, 北京 100029  
沈家豪 SHEN Jia-hao 北京中医药大学, 北京 100029  
期刊信息:《中国骨伤》2019年,第32卷,第8期,第721-726页
DOI:10.3969/j.issn.1003-0034.2019.08.009
基金项目:国家自然科学基金面上项目(编号:81373662);北京中医药大学研究生自主选题项目(编号:2017-JYB-XS-125)
中文摘要:

目的:探讨β-catenin与NF-κB信号通路在不同程度膝骨关节炎(knee osteoarthritis,KOA)模型大鼠滑膜组织中的表达情况。

方法:选取SPF级雄性大鼠48只,体重(200±20) g,采用随机数字表法将大鼠分为造模组(32只)、假手术组(8只)和对照组(8只)。造模组采用Hulth法建立KOA模型大鼠,并分别于造模后第2、4、8、12周取材处死8只,模拟轻度、早期、中度、重度KOA模型大鼠;假手术组仅切开膝关节囊后缝合排除手术因素干扰;对照组不做任何处理。观察各组大鼠动物行为、滑膜增生与软骨退变情况,采用实时荧光PCR检测各组大鼠滑膜组织中NF-κB信号通路及β-catenin的表达。

结果:成功建立KOA大鼠模型,取材过程中可见滑膜增生在轻度、早期KOA模型中表现明显,之后逐渐减少;而软骨退变在中度、重度KOA模型中表达明显,并随时间延长逐渐加重。PCR结果显示造模后4周组8.57±0.46、8周组4.23±0.09 β-catenin水平高于对照组1.18±0.22(P<0.05);2周组12.04±4.02、4周组8.54±2.13 TLR-2水平高于对照组0.88±0.15(P<0.05);TLR-4则在2周组5.04±0.93、4周组3.29±0.58及8周组1.63±0.12中表达显著高于对照组1.12±0.11(P<0.05),NF-κB在2周组10.15±2.04、4周组15.97±4.17、8周组7.69±1.48及12周组6.70±1.58中表达显著高于对照组1.26±0.27(P<0.05);IL-1β在4周组2.79±0.25、8周组2.46±0.32中表达显著高于对照组1.00±0.00(P<0.05)。

结论:在RNA表达层面,β-catenin与NF-κB信号通路均参与了大鼠KOA模型的滑膜炎症反应,两者在其下游炎性因子IL-1β的表达及KOA退变中可能共同发挥调控作用。
【关键词】骨关节炎,膝  滑膜炎  大鼠  Toll样受体
 
Expression and significance of β-catenin and NF-κB signaling pathway in knee osteoarthritis synovial inflammation
ABSTRACT  

Objective:To explore expression of β-catenin and NF-κB signaling pathway in synovial tissue of rats with different degrees of knee osteoarthritis (KOA).

Methods:Forty-eight SPF male rats weighed (200±20) g were randomly divided into three groups,namely model group (32 rats),sham operation group (8 rats) and control group (8 rats). KOA model rats were established by Hulth method,and 8 rats were killed at 2,4,8,12 weeks respectively after modeling,in order to establish KOA model rats with moderate,early,mild and severe degree. Sham operation group was only cut off capsule of knee joint and suture to exclude interference factor,control group was untreated. Behavior,synovial hyperplasia and cartilage degeneration of rats among each group were observed. Expression of NF-κB and signaling pathway and β-catenin in synovial tissue of rats were detected by real-time PCR.

Results:KOA rat model was successfully established,and synovial hyperplasia was observed in KOA model at mild and early degree,and then gradually decreased;while cartilage degeneration in the early moderate and severe KOA model was significantly expressed,and gradually aggravated with time. The results of PCR showed that expression of β-catenin in 4-week group (8.57±0.46) and 8-week group (4.23±0.09) were higher than those in control group (P<0.05);expression of TLR-2 in 2-week group (12.04±4.02) and 4-week group (8.54±2.13) were higher than those in control group(P<0.05),and TLR-4 in 2-week group(5.04±0.93),4-week group (3.29±0.58) and 8-week group (1.63±0.12) were higher than those in control group;expression of NF-κB was significantly higher in 2-week group (10.15±2.04),4-week group (15.97±4.17),8-week group (7.69±1.48) and 12-week group (6.70±1.58) than that in control group (P<0.05),and expression of IL-1β was significantly higher in 4-week group (2.79±0.25) and 8-week group (2.46±0.32) than that of control group (P<0.05).

Conclusion:On the RNA expression level,both of β-catenin and NF-κ B signaling pathways are involved in synovial inflammation in KOA model rats,and they play a regulatory role in expression of IL-1β,degeneration of KOA.
KEY WORDS  Osteoarthritis,knee  Synovitis  Rats  Toll-like receptors
 
引用本文,请按以下格式著录参考文献:
中文格式:张栋,王庆甫,张晓哲,阮安民,田宇,刘思婷,樊小燕,沈家豪.β-catenin与NF-κB信号通路在膝骨关节炎滑膜炎症中的表达特点及意义[J].中国骨伤,2019,32(8):721~726
英文格式:ZHANG Dong,WANG Qing-fu,ZHANG Xiao-zhe,RUAN An-min,TIAN Yu,LIU Si-ting,FAN Xiao-yan,SHEN Jia-hao.Expression and significance of β-catenin and NF-κB signaling pathway in knee osteoarthritis synovial inflammation[J].zhongguo gu shang / China J Orthop Trauma ,2019,32(8):721~726
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