Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin

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 e...

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Main Authors: Yufeng Zhang, Huaxin Deng, Zhiqiang Yang, Zhe Chen, Sheng Zhang, Yufan Zhu, Min Yang, Houcheng Zhong, Fuling Zhou, Yuanlong Xie, Lin Cai
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/5660927
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author Yufeng Zhang
Huaxin Deng
Zhiqiang Yang
Zhe Chen
Sheng Zhang
Yufan Zhu
Min Yang
Houcheng Zhong
Fuling Zhou
Yuanlong Xie
Lin Cai
author_facet Yufeng Zhang
Huaxin Deng
Zhiqiang Yang
Zhe Chen
Sheng Zhang
Yufan Zhu
Min Yang
Houcheng Zhong
Fuling Zhou
Yuanlong Xie
Lin Cai
author_sort Yufeng Zhang
collection DOAJ
description 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.
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spelling doaj-art-b2c28c1d3b9b4182a0e497b61da6ccda2025-02-03T01:07:06ZengWileyStem Cells International1687-96782021-01-01202110.1155/2021/5660927Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-CateninYufeng Zhang0Huaxin Deng1Zhiqiang Yang2Zhe Chen3Sheng Zhang4Yufan Zhu5Min Yang6Houcheng Zhong7Fuling Zhou8Yuanlong Xie9Lin Cai10Department of Spine Surgery and Musculoskeletal TumorDepartment of Spine SurgeryDepartment of Spine Surgery and Musculoskeletal TumorDepartment of Spine Surgery and Musculoskeletal TumorDepartment of Spine Surgery and Musculoskeletal TumorDepartment of Spine Surgery and Musculoskeletal TumorDepartment of Spine Surgery and Musculoskeletal TumorDepartment of Spine Surgery and Musculoskeletal TumorDepartment of HaematologyDepartment of Spine Surgery and Musculoskeletal TumorDepartment of Spine Surgery and Musculoskeletal TumorRadiation-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.http://dx.doi.org/10.1155/2021/5660927
spellingShingle Yufeng Zhang
Huaxin Deng
Zhiqiang Yang
Zhe Chen
Sheng Zhang
Yufan Zhu
Min Yang
Houcheng Zhong
Fuling Zhou
Yuanlong Xie
Lin Cai
Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin
Stem Cells International
title Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin
title_full Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin
title_fullStr Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin
title_full_unstemmed Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin
title_short Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin
title_sort treatment of radiation bone injury with transplanted hucb mscs via wnt β catenin
url http://dx.doi.org/10.1155/2021/5660927
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