Abstract
Radiation therapy is commonly used to treat cancer patients but exhibits adverse effects, including insufficiency fractures and bone loss. Epigenetic regulation plays an important role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, we reported local bone changes after single-dose exposure to 137CS irradiation in rats. Femur bone mineral density (BMD) and trabecular bone volume in the tibia were significantly decreased at 12 weeks after irradiation. Micro-CT results showed that tBMD, Tb.h and Tb.N were also significantly reduced at 12 weeks after irradiation exposure. ALP-positive OB.S/BS was decreased by 42.3% at 2 weeks after irradiation and was decreased by 50.8% at 12 weeks after exposure. In contrast to the decreased expression of Runx2 and BMP2, we found EZH2 expression was significantly increased at 2 weeks after single-dose 137CS irradiation in BMSCs. Together, our results demonstrated that single-dose 137CS irradiation induces BMD loss and the deterioration of bone microarchitecture in the rat skeleton. Furthermore, EZH2 expression increased and osteoblastogenesis decreased after irradiation. The underlying mechanisms warrant further investigation.
Highlights
To detect the relationship between EZH2 and irradiation-induced bone loss, we established a rat bone loss model using single-dose 137CS irradiation of the unilateral hindlimb
In addition to the bone loss and bone microarchitecture deterioration detected by micro-computed tomography at the site of exposure, we found decreased osteoblastogenesis and increased EZH2 expression in BMSCs after radiation
The results showed that the alkaline phosphatase (ALP)-positive OB.S/BS was decreased by 42.3% (P < 0.01) in the irradiated group compared to the control group at 2 weeks after irradiation (Fig. 2b)
Summary
To detect the relationship between EZH2 and irradiation-induced bone loss, we established a rat bone loss model using single-dose 137CS irradiation of the unilateral hindlimb. The maximum loading condition of the femur was significantly reduced at 12 weeks after irradiation and was decreased by 32.6% (P < 0.05) in the irradiated group compared to the control group (Fig. 1b). Femur bone mineral density (BMD), as determined by dual-energy X-ray absorptiometry (DXA), was reduced at 12 weeks post-irradiation and was markedly decreased by 8.8% (P < 0.05) compared to the control (Fig. 1c).
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