小型猪内翻膝内侧半月板的基因表达谱分析  

Gene expression profiling of the medial meniscus in a minipig model of varus knee

作　　者：方业汉 张键 黄晖[1] 周钢[1] 熊小龙[1] 林坚平[1] Fang Yehan;Zhang Jian;Huang Hui;Zhou Gang;Xiong Xiaolong;Lin Jianping(Orthopedics Center,Hainan General Hospital(Hainan Affiliated Hospital of Hainan Medical University),Haikou 570311,Hainan Province,China)

机构地区：[1]海南省人民医院(海南医学院附属海南医院)骨科中心,海南省海口市570311

出　　处：《中国组织工程研究》2021年第32期5109-5115,共7页Chinese Journal of Tissue Engineering Research

基　　金：海南省重点研发计划(ZDYF2017112),项目负责人:林坚平。

摘　　要：背景:内翻型膝关节骨性关节炎常合并有明显的内侧半月板病变,然而,其发生机制尚不明确。目的:寻找内翻膝继发内侧半月板病变的分子机制。方法:切除7只成年五指山小型猪右侧后肢前交叉韧带及外侧副韧带,造成内翻膝模型(实验侧),而左侧后肢行假手术(对照侧)。造模后26周时取内侧半月板,行基因芯片分析。实验中的所有程序均于2017-12-05经海南省人民医院医学伦理委员会审核批准,批准号Med-Eth-Re[2020]5。结果与结论:2组样本中共发现差异表达基因893个,其中上调537个,下调356个。差异最明显的生物进程包括性别决定、间质形态发生、一氧化氮生物合成过程的调节;细胞成分包括膜的固有成分、质膜的整体成分、内质网膜、核外膜-内质网膜网络;分子功能包括过渡金属离子结合、铁离子结合。信号通路有2型糖尿病、TRP通道的炎性介质调节、AMPK信号通路。提示内翻膝半月板基因表达出现明显变化,这些差异表达的基因可能揭露出内翻膝继发半月板病变的机制,将为其治疗和早期诊断提供潜在靶点。BACKGROUND: Varus-type osteoarthritis is often accompanied by obvious medial meniscus lesions. However, the underlying mechanism of its occurrence isyet unclear.OBJECTIVE: To explore the molecular mechanism of medial meniscus lesions secondary to varus knees.METHODS: The anterior cruciate ligament and lateral collateral ligament of the right rear limbs of seven Wuzhishan minipigs were resected to establish a varusknee model (experimental side), while the left hind legs were subjected to sham operation (control side). Medial meniscus samples were taken for a gene chipanalysis at 26 weeks after modeling. An ethic approval was obtained from the Medical Ethics Committee of Hainan General Hospital with an approval No. Med-Eth-Re[2020]5 on December 5, 2017.RESULTS AND CONCLUSION: The samples in the two groups showed significant differences in the gene expression. A total of 893 differentially expressed geneswere found, in which 537 were upregulated and 356 were downregulated. The significantly affected biological processes included sex determination, interstitialmorphogenesis, and regulation of nitric oxide biosynthetic process. The significantly affected cellular components included intrinsic component of membrane,integral component of plasma membrane, endoplasmic reticulum membrane, and epinuclear membrane-endoplasmic reticulum network. The significantlyaffected molecular functions included transition metal ion binding and iron ion binding. The significantly affected pathways included type II diabetes mellitus,inflammatory mediator regulation of TRP channels, and AMPK signaling pathway. These findings suggest significant changes in gene expression of varus kneemeniscus, and these differentially expressed genes may reveal the mechanism of medial meniscus lesions secondary to varus knee, providing a potential targetfor its treatment and early diagnosis.

关 键 词：内翻膝 半月板 五指山小型猪 基因芯片分析 基因表达谱 差异表达基因 分子机制 实验研究 

分 类 号：R446.1[医药卫生—诊断学] R318[医药卫生—临床医学]