Background: Osteoporosis is a common endocrine metabolic bone disease, which may lead to severe consequences. However, the unknown molecular mechanism of osteoporosis, the observable side effects of present treatments and the inability to fundamentally improve bone metabolism seriously restrict the impact of prevention and treatment. The study aims to identify potential biomarkers from osteoclast progenitors, specifically peripheral blood monocytes on predicting the osteoporotic phenotype.
Methods: Datasets were obtained from Gene Expression Omnibus (GEO). Based on the differentially expressed genes (DEGs) and GSEA results, GO and KEGG analyses were performed using the DAVID database and Metascape database. PPI network, TF network, drug-gene interaction network, and ceRNA network were established to determine the hub genes. Its osteogenesis, migration, and proliferation abilities in bone marrow mesenchymal stem cells (BMSCs) were validated through RT-qPCR, WB, ALP staining, VK staining, wound healing assay, transwell assay, and CCK-8 assay.
Results: A total of 63 significant DEGs were screened. Functional and pathway enrichment analysis discovered that the functions of the significant DEGs (SDEGs) are mainly related to immunity and metal ions. A comprehensive evaluation of all the network analyses, PMAIP1 was defined as osteoporosis's core gene. This conclusion was further confirmed in clinical cohort data. A series of experiments demonstrated that the PMAIP1 gene can promote the osteogenesis, migration and proliferation of BMSC cells.
Conclusions: All of these outcomes showed a new theoretical basis for further research in the treatment of osteoporosis, and PMAIP1 was identified as a potential biomarker for osteoporosis diagnosis and treatment.
Keywords: BMSC; ceRNA; diagnosis; osteoporosis; transcription factors.