Article Summary
杨春生,阿迪拉·迪里夏提,王宝兰,张铁成,武恒敏.生物钟和细胞周期在膝骨关节炎软骨中的相关性研究[J].现代生物医学进展英文版,2024,(6):1044-1049.
生物钟和细胞周期在膝骨关节炎软骨中的相关性研究
Study on the Correlation between Biological Clock and Cell Cycle in Knee Osteoarthritis Cartilage
Received:August 24, 2023  Revised:September 17, 2023
DOI:10.13241/j.cnki.pmb.2024.06.007
中文关键词: 骨关节炎  关节软骨  生物钟  细胞周期
英文关键词: Knee osteoarthritis  Articular cartilage  Biological clock  Cell cycle
基金项目:青年科研起航专项基金(2022YFY-QKQN-32);康复医学四川省重点实验室开放课题 (KFYXSZDSYS-10)
Author NameAffiliationE-mail
杨春生 新疆医科大学第一附属医院康复医学科 新疆 乌鲁木齐 830000 yc321456@qq.com 
阿迪拉·迪里夏提 新疆医科大学药学院 新疆 乌鲁木齐 830000  
王宝兰 新疆医科大学第一附属医院康复医学科 新疆 乌鲁木齐 830000  
张铁成 新疆医科大学第一附属医院康复医学科 新疆 乌鲁木齐 830000  
武恒敏 新疆医科大学第一附属医院康复医学科 新疆 乌鲁木齐 830000  
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中文摘要:
      摘要 目的:本研究的目的主要是探讨生物钟、细胞周期相关基因在膝骨关节炎(Knee Osteoarthritis,KOA)和正常软骨中的表达差异、相关性和作用。方法:选取KOA接受膝关节置换手术治疗的患者60例,收集术后胫骨平台和股骨内外侧髁软骨,将肉眼观察明显受损和宏观上正常的关节软骨,分为骨关节炎组(Osteoarthritis,OA)和相对正常组(Normal)。采用H.E.染色和番红固绿法染色,观察软骨组织病理变化。逆转录聚合酶链反应法检测BMAL1、PER1、CDK1、CCNB1、MMP13的mRNA表强度,分析它们在OA组和Normal之间的表达差异,并分析它们之间的相关性。免疫组织化学和蛋白免疫印迹法检测BMAL1、PER1、CDK1、CCNB1、MMP13蛋白的表达水平,进一步验证它们在OA组和Normal之间的表达差异。结果:相对于Normal组,OA组软骨表面不光滑,软骨变薄,基质破坏,蛋白聚糖丢失明显,软骨厚度降低。BMAL1在OA组表达量下降, CDK1、CCNB1、PER1、MMP13的mRNA表达量和蛋白表达水平明显增加,差异明显,P<0.05。相关性分析显示,BMAL1与CDK1、CCNB1、PER1、MMP13存在负相关,CDK1、CCNB1、PER1、MMP13之间存在正相关。结论:生物钟和细胞周期相关基因、蛋白在KOA软骨、正常软骨中存在表达差异和相关性,共同影响OA的发生、发展。
英文摘要:
      ABSTRACT Objective: The purpose of this study is to investigate the expression difference, correlation and function of circadian clock and cell cycle related genes in knee osteoarthritis (KOA) and normal cartilage. Methods: Sixty patients with KOA who underwent knee arthroplasty were selected. The tibial plateau and medial and lateral femoral condyle cartilage were collected after operation. The articular cartilage with obvious damage and normal macroscopic observation was divided into osteoarthritis group (OA group) and relatively normal group (Normal group). HE and safranine fast green staining were used to observe the pathological changes of cartilage tissue. The mRNA expression levels of BMAL1, PER1, CDK1, CCNB1 and MMP13 were detected by reverse transcription polymerase chain reaction (RT-PCR). The expression differences between OA group and Normal group were analyzed, and the correlation between them was analyzed. The expression levels of BMAL1, PER1, CDK1, CCNB1 and MMP13 proteins were detected by immunohistochemistry and Western blotting, and their expression differences between OA group and Normal group were further verified. Results: Compared with the Normal group, the cartilage surface of the OA group was not smooth, the cartilage became thinner, the matrix was destroyed, the proteoglycan was significantly lost, and the cartilage thickness was reduced. The expression of BMAL1 in OA group decreased, and the mRNA expression and protein expression levels of CDK1, CCNB1, PER1 and MMP13 increased significantly (P<0.05). Correlation analysis showed that BMAL1 was negatively correlated with CDK1, CCNB1, PER1 and MMP13, and there was a positive correlation between CDK1, CCNB1, PER1 and MMP13. Conclusion: There is a coupling relationship between clock and cell cycle in knee cartilage, and there is a difference in expression between KOA cartilage and normal cartilage. BMAL1 may be a protective factor for KOA, and CDK1, CCNB1, PER1 and MMP13 may be risk factors.
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