AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025200198
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ORIGINAL RESEARCH ARTICLE

Identification of MDM2 as a novel gene marker and key regulator of radiation-induced osteoblast damage

Jiguo Lin1† ,  Gang Zhao1† ,  Luping Wang1 ,  Chang Liu1 ,  Jie Feng1 ,  Chaonan Sun1 ,  Mingyu Wang2 ,  Yunpeng Dai2 ,  Jialu Zhang1 ,  Yannan Shen1* ,  Yunyun Cheng1*
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1 National Health Commission Key Laboratory of Radiobiology, College of Public Health, Jilin University, Changchun, Jilin, China
2 Department of Nuclear Medicine, China–Japan Union Hospital of Jilin University, Changchun, Jilin, China
†These authors contributed equally to this work.
EJMO, 025200198 https://doi.org/10.36922/EJMO025200198
Received: 17 May 2025 | Revised: 9 June 2025 | Accepted: 1 July 2025 | Published online: 21 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Bone injury is a common side effect and a long-term response in radiotherapy-induced osteoblast damage, often characterized by reduced osteoblast proliferation and differentiation. Despite its clinical relevance, studies on radiation-induced bone injury are limited, and the molecular mechanisms underlying ionizing radiation (IR)-induced osteoblast damage remain largely unclear.

Objectives: This study aimed to establish a radiation-induced osteoblast injury model, screen and identify related factors involved in the radiation injury of osteoblasts.

Methods: The optimal IR damage conditions were first determined by measuring cell proliferation, cycle, apoptosis, and differentiation and mineralization abilities in a radiation-induced osteoblast injury model. Subsequently, differentially expressed genes were screened through RNA sequencing of radiation-damaged MC3T3-E1 cells.

Results: Mouse double minute 2 homolog (MDM2) was the most significantly upregulated gene post-IR treatment, suggesting its key role in responses to IR. Meanwhile, cell apoptosis, cell cycle regulation, and several pathways, including the phosphoinositide 3-kinase/protein kinase B signaling pathway and signaling pathways involved in the cell cycle, were enriched. Furthermore, the role of MDM2 in radiation-induced osteoblast proliferation, differentiation, and DNA damage was investigated, followed by the identification of key pathway alterations under conditions of MDM2 knockdown and IR treatment.

Conclusion: MDM2 knockdown alleviated IR damage in MC3T3-E1 cells by promoting cell proliferation, reducing cell cycle arrest and apoptosis rates, and reversing osteoblast differentiation. These effects may be due to the alleviation of DNA damage.

Keywords
Ionizing radiation
Mouse double minute 2 homolog
Osteoblasts damage
DNA damage
Cell cycle
Funding
This work was supported by the Science and Technology Research and Planning Project of the Education Department of Jilin Province (JJKH20231240KJ), the 8th Young Science and Technology Talents Lift Project of Jilin Province (QT202426), the Bethune Project of Jilin University (2024B39) and the College Students “Innovation and Entrepreneurship Training (Innovation Training)” Program of Jilin University (202310183271, 202310183276).
Conflict of interest
The authors declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service, or company that could be construed as influencing the position presented in the manuscript entitled.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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