A Novel Molecular Regulatory Network in Bone Marrow Mesenchymal Stem Cells for Age-Related Osteoporosis

Background: This study evaluates the miRNA-mRNA regulatory networks that potentially influence the senescence mechanisms of bone marrow mesenchymal stem cells (BMSCs) in age-related osteoporosis (ARO). By identifying these networks, the study aims to offer new molecular markers and therapeutic targets for ARO. Methods: Five mRNA datasets were analyzed to identify common differentially expressed genes associated with senescence and osteoporosis. Seven hub genes were found to be enriched in the PI3K-Akt signaling pathway, and 22 hub miRNAs potentially regulating these genes. Primary BMSCs were harvested and cultured from seven younger, non-osteoporotic individuals and six older adults with osteoporosis. Expression levels of the hub genes and miRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Expression analysis showed that integrin subunit beta 3 (ITGB3), receptor tyrosine kinase ligand (KITLG), platelet-derived growth factor (PDGFB), and their associated regulatory miRNAs, exhibited significant differences between the two BMSC groups. Conclusion: A newly identified miRNA-mRNA regulatory network may mediate ARO via the PI3K-Akt signaling pathway in BMSCs. These molecular insights provide a foundation for potential therapeutic interventions targeting age-related osteoporosis.