Identification of MDM2 as a novel marker gene that modulates radiation-induced osteoblast damage

Bone injury is a common side effect of radiotherapy in tumors and is a long-term response after damage to osteoblasts, especially a reduction in osteoblast proliferation and differentiation. Currently, there are few studies on radiation-induced bone injury, and the molecules involved in ionizing radiation (IR)-induced osteoblast damage remain to be identified. In this study, the optimal IR damage conditions (8 Gy, 2.22 Gy/min) were first determined by measuring cell proliferation, the cell cycle, cell apoptosis and further cell differentiation and mineralization abilities in a radiation-induced osteoblast injury model. We subsequently screened 26 DEGs after RNA sequencing of the 8 Gy-irradiated MC3T3-E1 cells, which were involved mainly in DNA damage and repair, cell apoptotic progression and cell cycle regulation and involved several main pathways, including the PI3K-AKT signaling pathway, p53 signaling pathway and signaling pathway involved in the cell cycle and cell senescence. We focused on verifying the differentially expressed genes and confirmed that MDM2 was the most significantly upregulated gene after IR treatment, suggesting its key role in the response to IR. In addition, we addressed the functions of MDM2 in osteoblast proliferation, differentiation and DNA damage following MDM2 knockdown and IR treatment. In summary, knockdown of MDM2 alleviates IR-induced damage to MC3T3-E1 cells by promoting cell proliferation, reducing the cell cycle arrest rate and cell apoptosis rate, and reversing osteoblast differentiation, possibly through alleviation of DNA damage.