膝关节骨性关节炎中退变半月板的生物信息学分析

Bioinformatics analysis of degenerative meniscus in knee osteoarthritis

背景:半月板退变是膝关节骨性关节炎的表现之一,但其具体的分子机制仍不清楚。目的:探讨骨性关节炎退变半月板可能的分子生物学机制。方法:采用五指山猪的前交叉韧带切除法制备半月板退变猪模型,应用基因芯片技术检测在退变半月板组织中的差异表达基因,运用GO分析、通路分析和核心基因网络分析来发现相关的调控网络。结果与结论:①研究共检测到差异表达基因893个,其中cyp2c33,gcnt7,ncdn,exd3,MUC13,ppp1r3d,nphp3,upb1,CD81和prph差异表达最显著;②GO分析中显示的一氧化氮生物合成过程的调节、通路分析中发现的TRP通道、核心基因网络分析中检测出的MDFI基因等在引起半月板退变过程可能发挥关键作用;③上述数据说明,实验建立了可靠的半月板退变的动物模型,比较完整地揭示了骨性关节炎半月板退变基因谱的差异表达基因和所涉及的生物学过程和信号通路,为未来该疾病的诊断和治疗提供分子靶标。

BACKGROUND:Meniscus degeneration is one of the manifestations of knee osteoarthritis,but its specific molecular mechanism is still not very clear.OBJECTIVE:To explore the possible molecular biological mechanism of meniscus degeneration in knee osteoarthritis.METHODS:A meniscus degeneration model was prepared in Wuzhishan pigs through resection of the anterior cruciate ligament.Gene chip technology was used to detect differentially expressed genes in degenerated meniscus tissue.Gene oncology analysis,pathway analysis,and core gene network analysis were performed to discover relevant regulatory networks.RESULTS AND CONCLUSION:A total of 893 differentially expressed genes were detected in the study,of which cyp2c33,gcnt7,ncdn,exd3,MUC13,ppp1r3d,nphp3,upb1,CD81 and prph were differentially expressed most significantly.The regulation of nitric oxide biosynthetic process in gene oncology analysis,TRP channel in pathway analysis,and MDFI gene in core gene network analysis may play key roles to induce meniscus degeneration.In short,we have established a reliable animal model of meniscus degeneration,and more completely revealed the differentially expressed genes,biological processes and signal pathways related to meniscus degeneration after knee osteoarthritis.These will provide molecular targets for the diagnosis and treatment of the disease in the future.