Identification of key ferrotoposis-related therapeutic targets in icariin efficacy for postmenopausal osteoporosis treatment

Abstract

Introduction: Postmenopausal osteoporosis (PMOP) is a common disorder that threatens the health of postmenopausal women. Icariin (ICA), as a bioactive component extracted from the Chinese medicine Epimedium grandiflorum(Yinyanghuo), can reportedly relieve PMOP by reversing iron-overloaded bone loss. However, the detailed relationship between ferroptosis and icariin efficacy for PMOP treatment still needs further exploration. Methods: The PMOP model rats were established by performing ovariectomy and further validated by Micro-CT scanning. Potential ferroptosis-related differentially expressed genes in PMOP and ICA efficacy were identified via bioinformatics analyses. Finally, hub genes were further verified via real-time quantitative PCR. Results: In this study, 126 ferroptosis-related differentially expressed genes (DE-FRGs) in PMOP were first screened out. Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these genes were performed for the pursuit of further functional enrichment analysis. The protein-protein interaction (PPI) network was constructed to identify key modules within all the DE-FRGs. Then, DE-FRGs were further intersected with predicted target genes of ICA, and 11 genes were considered as potential icariin-regulated DE-FRGs in PMOP. After gene expression measurements of potential icariin-regulated DE-FRGs, five genes (PPARA, TGFB1, SRC, IL6, and SIRT1) were ultimately chosen as hub genes for ICA-regulated ferroptosis in PMOP treatment. Finally, the ROC curve and ceRNA network were established. Discussions: This study discovered potential ferroptosis-related therapeutic targets in ICA efficacy for PMOP treatment, which also contributes to the consideration of ICA as a novel therapy for PMOP.

Keywords

• Postmenopausal osteoporosis
• Ferroptosis
• Icariin
• Bioinformatics