Exploring the Mechanism of Action of Jintiange Capsules in Regulating SMSC-Exos miRNA and Articular Chondrocytes mRNA for the Treatment of Osteoarthritis in Rats Based on Transcriptome
OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA)and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos)and articular chondrocytes(ACs)in the treatment of OA based on high-throughput sequencing technology.METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation,bipedal balance difference experiment,mechanical foot reflex threshold,Micro-CT observation,and Safranin O-Fast Green staining.SMSCs and ACs were cultured in suitable concentration of drug-containing serum,and mRNA sequencing was performed on ACs in the control,model,and Jintiange capsules groups,as well as miRNA sequencing on SMSC-Exos.Differential expressed mRNAs and miRNAs were screened and target genes were predicted.The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes,and a miRNA-mRNA regulatory network was constructed using Cytoscape software.The expression trend analysis of common differential expressed genes was conducted,as well as the correlation analysis between differential expressed gene mRNA and miRNA,Micro-CT efficacy indicators,and differential expressed gene mRNA.RESULTS Under the pathological state of OA,the expression of miRNA-23a-3p,miRNA-342-3p,miRNA-146b-5p,miRNA-501-3p,and miRNA-214-3p were down-regulated,while miRNA-222-3p,miRNA-30e-3p,miRNA-676-3p,and miRNA-192-5p were up-regulated(P＜0.05).The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules.There was a certain correlation between Micro-CT efficacy indicators,mRNA and miRNA.CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA,and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10,Ntn1,Il1b,Tgm2,Megf10,1111,Cd40,Slc15a3,Pou2f2 and other genes.
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