Screening of key biomarkers in osteoporosis: Evidence from bioinformatic analysis

To analyze the expression characteristics of osteoporosis-related genes by bioinformatics and elucidate the pathogenesis of osteoporosis.

The differentially expressed genes (DEGs), microRNA (miRNA), and genes with differentially methylated regions (DMRS) in promoters were identified. The protein-protein interaction (PPI) network was constructed and performed. The Clue Gene Ontology analysis and miRNA-mRNA (messenger RNA) regulatory network were constructed using Cytoscape.

Fifty-nine DEGs, 10 differential miRNAs, and 2083 genes with DMRs were screened out. The Proteasome-Modulator (PSMD) family proteins and estrogen receptor 1 (ESR1) are vital for the PPI analysis of DEGs. The interaction network of the Smad3 protein showed that the degree of connection to ESR1, PSMD11, and transcription factor 4 (TCF4) is very high. Homo sapiens (hsa)-miR-106b-5p was differential and regulated TCF4 through building the miRNA-mRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of DEGs focused on vascular smooth muscle contraction, thyroid hormone signaling pathway, and estrogen signaling pathway. The Gene Ontology (GO) function analysis of genes with DMRs in promoters was primarily concentrated in the cell differentiation, positive regulation of CDP-diacylglycerol-serine O-phosphatidyltransferase activity, and positive regulation of C-palmitoyltransferase activity. The KEGG enrichment of genes with DMRs in promoters largely focused on glycerol phospholipid metabolism, histidine metabolism, Adenosine 5'-monophosphate-activated protein kinase signaling pathway, Hedgehog signaling pathway, and mRNA surveillance pathway.

Hsa-miRNA-106b-5p regulates bone formation and the pathogenesis of osteoporosis by controlling TCF4, and methylation modification of TCF4 can also affect the pathogenesis of osteoporosis.