Abstract
Radiation-induced bone injury (RIBI) is one of the complications after radiotherapy for malignant tumors. However, there are no effective measures for the treatment of RIBI in clinical practice, and the mechanism of RIBI is unclear. We use a single high-dose ionizing radiation (6Gy) to analyze the effect of radiotherapy on osteoblast function. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) were cocultured with irradiated osteoblasts to examine their therapeutic effects and mechanisms on osteoblast injury. The hUCB-MSC transplantation mouse model is used to confirm the in vivo role of hUCB-MSC treatment in radiation bone injury. Western blot analysis, qRT-PCR, immunohistochemistry, and immunofluorescence staining were used to analyze gene expression and angiogenesis. The apoptosis and migration of osteoblasts were measured by Hoechst staining, scratch test, and transwell. The differentiation of osteoblasts was measured by ALP and Alizarin red staining and transmission electron microscopy. The bone-related parameters of mice were evaluated by micro-CT analysis. We found that radiation can damage the DNA of osteoblasts; induce apoptosis; reduce the differentiation, migration, and adhesion of osteoblasts, leading to lipogenesis of bone marrow mesenchymal stem cells (BMSCs) and reducing the source of osteoblasts; and increase the number of osteoclasts in bone tissue, while MSC treatment prevents these changes. Our results reveal the inhibitory effect of radiation on osteoblast function. hUCB-MSCs can be used as a therapeutic target for the development of new therapeutic strategies for radiotherapy of bone injury diseases.
Highlights
Tumor radiation therapy is one of the common methods of treating tumors, especially malignant tumors, and radiation injury is one of the complications of radiation therapy
MC3T3-E1 cells treated with 0 Gy or 6 Gy irradiation were cultured for 48 hours, and the cells of each group were stained with Hoechst and quantitatively analyzed
The results showed that the Hoechst-positive cells increased in the osteoblasts treated with coculture of hUCB-MSCs instead of decreasing (Figure 2(a)), and the Hoechst-positive rate was significantly different between the two groups (Figure 2(b))
Summary
Tumor radiation therapy is one of the common methods of treating tumors, especially malignant tumors, and radiation injury is one of the complications of radiation therapy. Numerous facts have shown that it is more difficult for patients receiving radiotherapy to heal bone defects than normal patients, including damage to the function of bone cells during radiation intervention, fibrosis, necrosis, resorption lacuna, and increase of woven lamellar bone in bone tissue [4]. The reasons for these changes may be the damage of tissue blood vessels [5, 6] and the abnormal changes in the functions of osteoblasts
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