Cheng, Y.; Lin, J.; Zhao, G.; Liu, C.; Feng, J.; Sun, C.; Zhang, J.; Wang, L.; Shen, Y. Screening and Identification of Potentials Molecules Involved in the Radiation Induced Osteoblast Damage. Preprints2024, 2024071086. https://doi.org/10.20944/preprints202407.1086.v1
APA Style
Cheng, Y., Lin, J., Zhao, G., Liu, C., Feng, J., Sun, C., Zhang, J., Wang, L., & Shen, Y. (2024). Screening and Identification of Potentials Molecules Involved in the Radiation Induced Osteoblast Damage. Preprints. https://doi.org/10.20944/preprints202407.1086.v1
Chicago/Turabian Style
Cheng, Y., Luping Wang and Yannan Shen. 2024 "Screening and Identification of Potentials Molecules Involved in the Radiation Induced Osteoblast Damage" Preprints. https://doi.org/10.20944/preprints202407.1086.v1
Abstract
Bone injury is a common side effect of radiotherapy to tumors, which is a long-term response after damage to osteoblasts, especially reducing osteoblasts proliferation and differentiation. Currently, there are few studies on radiation-induced bone injury, the molecules involved in the ionizing radiation (IR) induced osteoblasts damage remain need to be excavated. In this study, the optimal IR damage conditions (8Gy, 2.22Gy/min) were firstly determined by measuring cell proliferation, cell cycle, cell apoptosis and further cell differentiation and mineralization abilities and the related genes (p-AKT, p-ERK1/2, cyclinB, BAX, BCL2, ALP, OPN, RUNX2, Collagen1) expression level changes in radiation-induced osteoblast injury model. Then, we screened 26 differentially expressed genes after the RNA-sequencing of the 8 Gy-irradiated MC3T3-E1 cells, and they were mainly involved in DNA damage and repair, cell apoptotic progress and cell cycle regulation, meanwhile, participated in several main pathway including PI3K-AKT signaling pathway, p53 signaling pathway and signaling pathway involved in cell cycle and cell senescence. We focused on verifying the differential expression genes and confirmed the MDM2, NOTCH1, CDKN1A and GCLC were upregulated after IR treatment, suggesting the key roles in the response of the IR. In addition, regarding on our sequencing results, the DNA damage and repair were also verified and the results suggested that IR induced DNA damage and repair in MC3T3-E1 cells. In summary, IR damaged MC3T3-E1 cells by inhibiting cell proliferation, impacting cell cycle process, inducing cell apoptosis and affecting the osteoblasts differentiation, which maybe due to the DNA damage and the differential expression of the key genes (MDM2, NOTCH1, CDKN1A and GCLC ).
Keywords
Ionizing radiation; osteoblasts damage; osteoblasts differentiation; DNA damage; cell cycle
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
