ABSTRACT
Objective: Previous studies showed the PRP have the therapeutic effects for KOA, but the more detail roles remained unclear and therefore this study was carried on to explore the deeper mechanisms for PRP. Methods: NRS and WOMAC scores were used to evaluate the clinical efficacy before surgery, 1 month and 6 months after surgery, and the postoperative joint structure changes (n = 24). Examination of pathology of the femoral condyle plate in rats using HE staining (n = 6); Angiogenesis experiments were used to investigate the effect of different groups of cell culture supernatants on the tubular structure formation capacity of HUVECs (n = 3). Observe the proliferation of chondrocytes using clonal formation experiments (n = 3). Western blot was used to analyze the PI3K/AKT signaling pathway and the expression of exosome-secretion-related proteins (n = 3). Results: In clinical studies, PRP can reduce patients' NRS and WOMAC scores and alleviate the progression of knee arthritis; In rat experiments, PRP reduced damage from knee arthritis and lowered Mankin's score. PRP improves tubular formation of HUVECs and the proliferation capacity of chondrocytes. Compared with the blank control group, the protein expression levels of PI3K, AKT, mTOR, P27, and cyclinD1 in the PRP group were increased. Compared with the PRP group, the protein expression levels of PI3K, AKT, mTOR, P27, and cyclinD1 in the PRP+Axitinib group supplemented with VEGFRs inhibitor and PI3K inhibitor group were significantly decreased. The effect of the LY294002 +PRP group was better than that of the above groups. Macrophage-derived exosomes activate HIF-1a and COX-2 in endothelial cells to promote chondrocyte repair of KOA. Conclusion: PRP can promote chondrocytes proliferation and repair by activating the PI3K/AKT signaling pathway, thereby exerting anti-OA effects. It provides new targets and methods for the clinical treatment of OA.
ABSTRACT
PURPOSE: Ewing's sarcoma (ES) is a highly aggressive malignant bone and soft tissue neoplasm. The purpose of our study was to identify candidate biomarkers of ES and uncover their potential molecular mechanisms. METHODS: The gene expression profiles of GSE45544 and GSE73166 were downloaded from Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed based on the Database for Annotation, Visualization and Integrated Discovery (DAVID) database, protein-protein interaction (PPI) network was constructed, and hub genes of the differentially expressed genes (DEGs) were identified by Cytoscape software. RESULTS: 586 DEGs in total were identified in ES, and the top up-regulated genes were extremely potent as ES biomarkers. GO function analysis data showed that these DEGs were significantly enriched in DNA translation, nucleus, and protein binding. KEGG pathway analysis revealed that DEGs were enriched in the pathways involved in cancer, HTLV-I infection, viral carcinogenesis, ribosome, and cell cycle. PPI network showed that most of the hub genes were for ribosomal proteins, associated in some way with the biological process of ES. CONCLUSIONS: In conclusion, we identified the DEGs and hub genes which could promote our comprehension of detailed mechanisms involved in the development of ES.
