LAUSR

Osteoporosis is characterized by lowing bone mineral density. This study aimed to investigate the genes, miRNAs, pathways, and miRNA-gene interaction pairs involved in the pathogenesis of female osteoporosis. The differentially expressed genes (DEGs, GSE62402), differentially expressed miRNAs (DEmiRNAs, GSE63446), and differentially methylated genes (GSE62588) between females with low- and high-hip bone mineral density were identified. Genes common to DEGs, differentially methylated genes, DEmiRNAs' targets, and osteoporosis-related genes were retained and used to construct the miRNA-mRNA-pathway regulatory network. The expression of hub nodes was validated in microarray datasets (genes in GSE56116 and miRNAs in GSE93883). Thirty-four DEmiRNAs and 179 DEGs with opposite expression-methylation profiles were identified. Functional enrichment analysis showed that DEGs were associated with pathways including "hsa00380:Tryptophan metabolism," "hsa04670:Leukocyte transendothelial migration," "hsa04630:Jak-STAT signaling pathway," and "hsa04062:Chemokine signaling pathway." The miRNA-mRNA-pathway network included 10 DEGs, 9 miRNAs, and 4 osteoporosis-related pathways. The miRNA-gene-pathway axes including hsa-miR-27b-5p/3p-IFNAR1-hsa04630, hsa-miR-30a-5p/3p-IFNAR1-hsa04630, hsa-miR-30a-5p/3p-ALDH2-hsa00380, and hsa-miR-194-5p/3p-NCF2-hsa04670 were included in the network. Microarray validation showed that IFNAR1, NCF2, and ALDH2 were upregulated, and hsa-miR-30a-3p/5p, hsa-miR-194-3p/5p, hsa-miR-27b-3p/5p, and hsa-miR-34a-3p were downregulated in osteoporotic samples compared with control. Axes including hsa-miR-27b/30a-IFNAR1-Jak-STAT signaling pathway, hsa-miR-30a-ALDH2-Tryptophan metabolism, and hsa-miR-194-NCF2-Leukocyte transendothelial migration were involved in osteoporosis pathogenesis.