Investigation on the molecular mechanism of SPA interference with osteogenic differentiation of bone marrow mesenchymal stem cells

Abstract

The binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow derived mesenchymal stem cells (BMSC) has the ability to differentiate into bone, fat and cartilage. Hence, it was vital to analyze the molecular mechanism of SPA affecting osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA interfered BMSC. Protein-protein interaction (PPI) network of DEGs was established to screen biomarkers associated with BMSC with SPA interference. ROC curve was plotted to evaluate the ability of biomarkers to distinguish between two groups of samples. We finally performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified via hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly distinguish normal differentiated and SPA interfered BMSC. Moreover, we found that these biomarkers was mainly enriched in the ‘Pyrimidine metabolism’ pathway. We also constructed ‘71 circRNAs-14 miRNAs-5 mRNAs’ and ‘10 lncRNAs-5 miRNAs-2 mRNAs’ networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significant lower expression of six biomarkers in SPA interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) related to SPA interfered BMSC, which laid a theoretical foundation for exploring the key factors of SPA affecting osteogenic differentiation.