Analysis and Validation of Hub Genes in Blood Monocytes of Postmenopausal Osteoporosis Patients

Osteoporosis is a common systemic bone disease caused by the imbalance between osteogenic activity and osteoclastic activity. Aged women are at higher risk of osteoporosis, partly because of estrogen deficiency. However, the underlying mechanism of how estrogen deficiency affects osteoclast activity has not yet been well elucidated. In this study, GSE2208 and GSE56815 datasets were downloaded from GEO database with 25 PreH BMD women and 25 PostL BMD women in total. The RRA algorithm determined 38 downregulated DEGs and 30 upregulated DEGs. Through GO analysis, we found that downregulated DEGs were mainly enriched in myeloid cell differentiation, cytokine-related functions while upregulated DEGs enriched in immune-related biological processes; pathways like Notch signaling and MAPK activation were found in KEGG/Rectome pathway database; a PPI network which contains 66 nodes and 91 edges was constructed and three Modules were obtained by Mcode; Correlation analysis helped us to find highly correlated genes in each module. Moreover, three hub genes FOS, PTPN6, and CTSD were captured by Cytohubba. Finally, the hub genes were further confirmed in blood monocytes of ovariectomy (OVX) rats by real-time PCR assay. In conclusion, the integrative bioinformatics analysis and real-time PCR analysis were utilized to offer fresh light into the role of monocytes in premenopausal osteoporosis and identified FOS, PTPN6, and CTSD as potential biomarkers for postmenopausal osteoporosis.

Automated summary

In this study, the impact of estrogen deficiency on osteoclast activity was investigated through integrative bioinformatics analysis. The downregulated and upregulated differentially expressed genes (DEGs) were identified using the RRA algorithm. GO analysis revealed enrichment of downregulated DEGs in myeloid cell differentiation and cytokine-related functions, while upregulated DEGs were enriched in immune-related biological processes. KEGG/Rectome pathway analysis identified Notch signaling and MAPK activation pathways. A PPI network was constructed, and three modules were obtained. Correlation analysis identified highly correlated genes in each module. Furthermore, three hub genes (FOS, PTPN6, and CTSD) were identified as potential biomarkers for postmenopausal osteoporosis and were validated using real-time PCR assay in blood monocytes of OVX rats.