Abstract
BACKGROUND AND AIMS: This study aimed to construct a miRNA-mRNA network in OF and explored the effect of the hsa-miR-32-3p/TNFSF11 axis on osteoclast function. METHODS: GSE70318 and GSE74209 datasets were used to filter the differentially expressed miRNAs in OF. Then, the targets of these miRNAs intersected with the disease genes of OF. The target genes were annotated using GO terms and KEGG pathway enrichment analysis. The network for miRNA-gene-top 30 GO terms/top 20 pathways was drawn. Sankey diagrams were drawn for Parathyroid hormone synthesis, secretion, and action pathway (hsa04928) and ossification (GO:0001503) related to osteoporotic fracture. The hsa-miR-32-3p/TNFSF11 axis was selected for expression and functional verification. RESULTS: A total of 21 differentially expressed miRNAs in OF were obtained by analyzing GSE70318 and GSE74209 datasets. A total of 36 genes were related to OF among the miRNA-targets. The genes were enriched in GO terms and KEGG pathways related to OF. Parathyroid hormone synthesis, secretion, and action pathway (hsa04928) and ossification proposed that the hsa-miR-32-3p/TNFSF11 axis may be involved in OF. The expression level of hsa-miR-32-3p was decreased in patients with low bone mineral density (BMD) and fracture, while the expression level of TNFSF11 mRNA was increased. Hsa-miR-32-3p complementarily bound with TNFSF11. Hsa-miR-32-3p inhibited osteoclast activation, while TNFSF11 promoted osteoclast activation. CONCLUSIONS: The miRNA-mRNA network in OF proposed the TNFSF11 as a downstream target of hsa-miR-32-3p. The hsa-miR-32-3p/TNFSF11 axis was involved in the regulation of osteoclast activity. CLINICAL TRIAL NUMBER: Not applicable.