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Investigation on the molecular mechanism of SPA interference with osteogenic differentiation of bone marrow
Hong-Jie Wen1,2, Shou-Yan Zhu1,2, Hua-Gang Yang1,2
1Department of Orthopaedic and Trauma, The Affiliated Hospital of Yunnan University, Kunming, China.
Abstract:
Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on 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 SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were 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 significantly lower expression of six biomarkers in the 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 provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.
Insights
Staphylococcus aureus protein A (SPA) interferes with bone marrow-derived mesenchymal stem cell (BMSC) differentiation. Six key biomarkers were identified, offering insights into SPA
Area of Science:
- Molecular Biology
- Stem Cell Biology
- Biomarker Discovery
Background:
- Staphylococcus aureus protein A (SPA) binding to osteoblasts inhibits bone formation.
- Bone marrow-derived mesenchymal stem cells (BMSCs) are crucial for bone regeneration.
- The molecular mechanisms of SPA's impact on osteogenic differentiation require elucidation.
Purpose of the Study:
- To analyze the molecular mechanisms underlying SPA's effect on osteogenic differentiation of BMSCs.
- To identify potential biomarkers for SPA-interfered BMSC differentiation.
Main Methods:
- Transcriptome sequencing to identify differentially expressed genes (DEGs) in SPA-interfered BMSCs.
- Protein-protein interaction (PPI) network analysis to screen for hub biomarkers.
- Receiver operating characteristic (ROC) curve analysis for biomarker validation.
- Gene Set Enrichment Analysis (GSEA) and regulatory network construction (circRNA, miRNA, lncRNA).
Main Results:
- 321 DEGs were identified, leading to the discovery of six key biomarkers: Cenpf, Kntc1, Nek2, Asf1b, Troap, and Kif14.
- These biomarkers effectively discriminated between normal and SPA-interfered BMSCs.
- Biomarkers were predominantly enriched in the pyrimidine metabolism pathway.
- Novel circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA regulatory networks were established.
- RT-qPCR confirmed significantly lower expression of the six biomarkers in SPA-interfered BMSCs.
Conclusions:
- Six identified biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap, Kif14) are significantly associated with SPA-interfered BMSC differentiation.
- These biomarkers provide a theoretical foundation for understanding the key factors affected by SPA during osteogenic differentiation.
- The findings contribute to potential therapeutic strategies targeting bone formation impairment.
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