Identification of endoplasmic reticulum stress and mitochondrial dysfunction related biomarkers in osteoporosis.

Abstract

Background: Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction (MD) involved in bone metabolism disorders. However, the particular mechanisms of ERS and MD related genes (ERS&MDRGs) in osteoporosis (OP) have not been elucidated. In present study, biomarkers related to ERS and MD in OP were identified.

Methods: Differentially expressed genes (DEGs) were obtained based on GEO dataset. ERS&MDRGs were derived from Genecard database. Initially, ERS&MD related DEGs (ERS&MDRDEGs) were obtained by overlapping DEGs and ERS&MDRGs. The key module was screened by WGCNA. The intersection of ERS&MDRDEGs and key module was screened by machine learning to obtain key genes. Then, receiver operating characteristic curve (ROC) was drawn to calculated diagnostic accuracy of key genes. The ssGSEA and Cibersort algorithms were performed to analyze immune cell infiltration. The miRNA-mRNA-TF network were draw by cytoscape software. Moleculaer docking and DGIdb database were employed for screening potential drugs. Finally, the expression of key genes was verified by qRT-PCR.

Results: The 122 ERS&MDRDEGs were obtained by preliminary screening. ERS&MDRDEGs were mainly enriched in lipid metabolism, calcium ion transport, and ossification. The 5 key genes were identified, including AAAS, ESR1, SLC12A2, TAF15, and VAMP2. Immune infiltration analysis showed monocyte and macrophage were different between OP and control groups. The miRNA-mRNA-TF regulatory network indicated has-miR-625-5p, has-miR-296-3p, CTCT and EP300 as potential regulatory targets. The 2 potential small molecule drugs, namely bumetanide and elacestrant were screened. The expression of AAAS, ESR1, VAMP2 were higher, and SLC12A2 and TAF15 were lower in OP than control group.

Conclusion: This research identified 5 key genes AAAS, ESR1, SLC12A2, TAF15 and VAMP2. Bumetanide and elacestrant were potential drugs. These findings provided valuable insights into the pathophysiology of OP and the development of new therapeutic strategies.