| Background and Objective:OA is not only a joint cartilage disease,but also a disease of the entire joint.Synovial tissue inflammation may be an important cause of OA.Meniscus degeneration is one of the characteristics of OA and has a close relationship with OA.At present,OA research focuses on articular cartilage and does not pay much attention to synovium and meniscus.Studying the basic pathological process of OA synovium and meniscus will help to further understand the pathogenesis of OA.In this study,we downloaded GSE82107 microarray data and established a bioinformatics analysis of synovial tissue to explore the molecular mechanism of synovitis in OA.In addition,we established an animal model of meniscus degeneration in OA and performed bioinformatics analysis of meniscus tissue.Studies have sought to identify the causative molecules associated with synovitis and meniscus degeneration in OA.Methods:Gene chip data GSE82107 was input into GCBI analysis platform for in-depth bioinformatics analysis.GSE82107 included 10 cases in OA group(experimental group)and 7 cases in HC group(Health Control group,normal control group).In addition,14 healthy Wuzhishan miniature pigs were divided into experimental group and control group,7 in each group.The experimental group underwent left anterior cruciate ligament resection,and the control group underwent left knee sham operation.All pigs were euthanized and fed the medial meniscus 24 weeks after feeding.Histopathological examination confirmed the establishment of the OA model and the establishment of meniscus degeneration.After extracting RNA from the meniscus tissues,the relevant key genetic information were obtained after the whole gene profile and GCBI analysis,and the related genes were verified by RT-PCR.After the degeneration meniscus fibrochondrocytes were isolated and cultured,the experiment was divided into miR-335-5P mimics group,inhibitor group,mimics-NC group,inhibitor-NC group,the mRNA and protein expression levels of miR-335-5P,MDFI and MMP-13 were detected respectively.Finally,DEG combined miRNA analysis of synovitis and degeneration meniscus was performed.Results:Bioinformatics analysis of OA synovitis detected 1941 differentially expressed genes(DEG),including 1471 up-regulated genes and 470 down-regulated genes.The key genetic information are genes such as NRAS,SPHK2,FOS,CXCR4,PLD1,GNAI2 and PLA2G4F and their related biological processes and pathways(such as apoptosis,MAPK signalling pathway and cancer signalling).Experimental studies on the mechanism of knee meniscus degeneration found key genetic information such as regulation of nitric oxide biosynthetic process,Inflammatory mediator regulation of TRP channels,MDFI,UBC,hsa-miR-335-5p,Sp1 and NKT cell.In addition,miR-335-5p was differentially expressed in the degenerative meniscus,which positively regulated the mRNA expression levels of MDFI and MMP13,and positively regulated the protein expression levels of MDFI and MMP13.DEG combined miRNA analysis of synovitis and degenerative meniscus had the highest number of connections between miR-335-5p and DEG.Conclusion:Genes such as NRAS,SPHK2,FOS,CXCR4,PLD1,GNAI2,and PLA2G4F in OA synovitis and their related biological processes and pathways(such as apoptosis,MAPK signaling pathway,and cancer signaling pathway)may represent potential for OA treatment and diagnosis aims.The Wuzhishan pig OA model provides a reasonable and reliable animal experiment model for the study of meniscus degeneration.The key genetic information that may be involved in OA meniscus degeneration are:regulation of nitric oxide biosynthetic process,Inflammatory mediator regulation of TRP channels,MDFI,UBC,hsa-miR-335-5p,Spl,and NKT cell,among which inflammatory mechanisms may play a role Key role.miR-335-5p can promote MDFI,MMP13 transcription and protein synthesis,and play a potential role in promoting the onset of meniscus degeneration.miR-335-5p is a common regulatory molecule of synovitis and meniscus in OA,and may provide a new target for the treatment of OA. |
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