Transcriptomic Profiling and miRNA-Target Gene Network Construction Reveals Epigenetic Drivers of Glucocorticoid-Induced Osteoporosis
Abstract
BACKGROUND
Glucocorticoid-induced osteoporosis (GIO) is a common form of secondary osteoporosis caused by prolonged glucocorticoid (GC) use. Its molecular mechanisms, particularly the role of miRNAs and gene regulatory networks in osteoblast dysfunction and bone remodeling, remain incompletely understood.
METHODS
Gene expression data from GC-treated mouse osteoblasts (GSE291858) were analyzed using the IDEP 2.0 pipeline and DESeq2 to identify differentially expressed genes (DEGs). Functional enrichment analyses were performed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The miRNA targets of the transcription factor KLF4 were predicted using miRDB v6.0, and the miRNA-TF-gene networks were constructed using JASPAR, STRING, and Cytoscape. Hub genes were identified using cytoHubba, and disease associations were validated with the Human microRNA Disease Database (HMDD).
RESULTS
The analysis revealed significant transcriptional changes between GC-treated and control osteoblasts. The DEGs were enriched in immune signaling, osteoclast differentiation, and vascular smooth muscle contraction pathways. KLF4 emerged as a central hub gene, regulated by 38 high-confidence miRNAs, including hsa-miR-32-5p, hsa-miR-92b-3p, and hsa-miR-7-5p. Network analysis highlighted interactions with STAT3, IL6, JUN, and VEGFA, linking inflammatory, proliferative, and osteogenic processes. PCA and clustering confirmed distinct expression profiles between treated…
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