Zhang Yufeng, Deng Huaxin, Yang Zhiqiang, Chen Zhe, Zhang Sheng, Zhu Yufan, Yang Min, Zhong Houcheng, Zhou Fuling, Xie Yuanlong, Cai Lin
Department of Spine Surgery and Musculoskeletal Tumor, Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Spine Surgery, The Central Hospital of Yongzhou, Yongzhou, China.
Stem Cells Int. 2021 Nov 28;2021:5660927. doi: 10.1155/2021/5660927. eCollection 2021.
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.
放射性骨损伤（RIBI）是恶性肿瘤放疗后的并发症之一。然而，临床实践中尚无治疗RIBI的有效措施，且RIBI的机制尚不清楚。我们采用单次大剂量电离辐射（6Gy）来分析放疗对成骨细胞功能的影响。将人脐带血间充质干细胞（hUCB-MSCs）与受照射的成骨细胞共培养，以研究其对成骨细胞损伤的治疗作用及机制。利用hUCB-MSC移植小鼠模型来证实hUCB-MSC治疗在放射性骨损伤中的体内作用。采用蛋白质免疫印迹分析、qRT-PCR、免疫组织化学和免疫荧光染色来分析基因表达和血管生成。通过Hoechst染色、划痕试验和Transwell实验检测成骨细胞的凋亡和迁移。通过碱性磷酸酶和茜素红染色以及透射电子显微镜检测成骨细胞的分化。通过显微CT分析评估小鼠的骨相关参数。我们发现辐射可损伤成骨细胞的DNA；诱导凋亡；降低成骨细胞的分化、迁移和黏附，导致骨髓间充质干细胞（BMSCs）脂肪生成并减少成骨细胞来源；增加骨组织中破骨细胞数量，而间充质干细胞治疗可防止这些变化。我们的结果揭示了辐射对成骨细胞功能的抑制作用。hUCB-MSCs可作为开发骨损伤疾病放疗新治疗策略的治疗靶点。
