Transcriptome sequencing-based study on the mechanism of action of Jintiange capsules(金天格胶囊)in regulating synovial mesenchymal stem cells exosomal miRNA and articular chondrocytes mRNA for the treatment of osteoarthritis

OBJECTIVE: To corroborate the efficacy of Jintiange capsules(JTGs)( 金天格胶囊) in the treatment of osteoarthritis(OA) by exploring the potential mechanism of action of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) through transcriptome sequencing(RNA-seq). METHODS: Type Ⅱ collagenase was used to induce OA in rats. The efficacy of JTGs was confirmed by macroscopic observation of articular cartilage, micro-CT observation, and safranin fast green staining. After SMSC-Exos and ACs were qualified, RNA-seq was used to screen differentially expressed mi RNAs and m RNAs. The target genes of differentially expressed mi RNAs in Synovial mesenchymal stem cells(SMSCs) were predicted based on the multi Mi R R package. The codifferentially expressed genes of SMSC-Exos and ACs were obtained by venny 2.1.0. The mi RNA-m RNA regulatory network was constructed by Cytoscape software. Based on the Omic Share platform, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed on the m RNA regulated by key mi RNAs. Expression trend analysis was performed for co-differentially expressed genes. Correlation analysis was performed on micro-CT efficacy indicators, co-differentially expressed genes mRNA and miRNA. RESULTS: The efficacy of each administration group of JTGs was significant compared with the model group. SMSC-Exos and ACs were identified by their characteristics. The expression of rno-mi R-23a-3p, rnomi R-342-3p, rno-miR-146b-5p, rno-miR-501-3p, rnomiR-214-3p was down-regulated in OA pathological state, and the expression of rno-mi R-222-3p, rno-mi R-30e-3p, rno-mi R-676, and rno-miR-192-5p expression was upregulated, and the expression of all these mi RNAs was reversed after the intervention with JTGs containing serum. The co-differentially expressed genes were enriched in the interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, transforming growth factor-β signaling pathway, etc. The expression trends of Ccl7, Akap12, Grem2, Egln3, Arhgdib, Ccl20, Mmp12, Pla2g2a, and Nr4a1 were significant. There was a correlation between micro-CT pharmacodynamic index, m RNA, and mi RNA. CONCLUSION: JTGs can improve the degeneration of joint cartilage and achieve the purpose of cartilage protection, which can be used for the treatment of OA. SMSCs-related mi RNA expression profiles were significantly altered after the intervention with JTGs containing serum. The 9 co-differentially expressed genes may be the key targets for the efficacy of JTGs in the treatment of OA rats, which can be used for subsequent validation.