Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus
Nonunion and delayed union are common complications of diabetes mellitus that pose a serious health threat to people. There are many approaches that have been used to improve bone fracture healing. Recently, exosomes have been regarded as promising medical biomaterials for improving fracture healing...
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MDPI AG
2023-03-01
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author | Dong Zhang Weidong Xiao Changjiang Liu Zheng Wang Yuhang Liu Yifeng Yu Chao Jian Aixi Yu |
author_facet | Dong Zhang Weidong Xiao Changjiang Liu Zheng Wang Yuhang Liu Yifeng Yu Chao Jian Aixi Yu |
author_sort | Dong Zhang |
collection | DOAJ |
description | Nonunion and delayed union are common complications of diabetes mellitus that pose a serious health threat to people. There are many approaches that have been used to improve bone fracture healing. Recently, exosomes have been regarded as promising medical biomaterials for improving fracture healing. However, whether exosomes derived from adipose stem cells can promote bone fracture healing in diabetes mellitus remains unclear. In this study, adipose stem cells (ASCs) and exosomes derived from adipose stem cells (ASCs-exos) are isolated and identified. Additionally, we evaluate the in vitro and in vivo effects of ASCs-exos on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone repair and the regeneration in a rat model of nonunion via Western blotting, immunofluorescence assay, ALP staining, alizarin red staining, radiographic examination and histological analysis. Compared with controls, ASCs-exos promoted BMSC osteogenic differentiation. Additionally, the results of Western blotting, radiographic examination and histological analysis show that ASCs-exos improve the ability for fracture repair in the rat model of nonunion bone fracture healing. Moreover, our results further proved that ASCs-exos play a role in activating the Wnt3a/β-catenin signaling pathway, which facilitates the osteogenic differentiation of BMSCs. All these results show that ASCs-exos enhance the osteogenic potential of BMSCs by activating the Wnt/β-catenin signaling pathway, and also facilitate the ability for bone repair and regeneration in vivo, which provides a novel direction for fracture nonunion in diabetes mellitus treatment. |
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spelling | doaj.art-45c5ebfbc03e43489fca4364f3c3a6232023-11-17T07:54:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01245485210.3390/ijms24054852Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes MellitusDong Zhang0Weidong Xiao1Changjiang Liu2Zheng Wang3Yuhang Liu4Yifeng Yu5Chao Jian6Aixi Yu7Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430000, ChinaNonunion and delayed union are common complications of diabetes mellitus that pose a serious health threat to people. There are many approaches that have been used to improve bone fracture healing. Recently, exosomes have been regarded as promising medical biomaterials for improving fracture healing. However, whether exosomes derived from adipose stem cells can promote bone fracture healing in diabetes mellitus remains unclear. In this study, adipose stem cells (ASCs) and exosomes derived from adipose stem cells (ASCs-exos) are isolated and identified. Additionally, we evaluate the in vitro and in vivo effects of ASCs-exos on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone repair and the regeneration in a rat model of nonunion via Western blotting, immunofluorescence assay, ALP staining, alizarin red staining, radiographic examination and histological analysis. Compared with controls, ASCs-exos promoted BMSC osteogenic differentiation. Additionally, the results of Western blotting, radiographic examination and histological analysis show that ASCs-exos improve the ability for fracture repair in the rat model of nonunion bone fracture healing. Moreover, our results further proved that ASCs-exos play a role in activating the Wnt3a/β-catenin signaling pathway, which facilitates the osteogenic differentiation of BMSCs. All these results show that ASCs-exos enhance the osteogenic potential of BMSCs by activating the Wnt/β-catenin signaling pathway, and also facilitate the ability for bone repair and regeneration in vivo, which provides a novel direction for fracture nonunion in diabetes mellitus treatment.https://www.mdpi.com/1422-0067/24/5/4852exosomeASCsfracturenonunionosteogenesisdiabetes mellitus |
spellingShingle | Dong Zhang Weidong Xiao Changjiang Liu Zheng Wang Yuhang Liu Yifeng Yu Chao Jian Aixi Yu Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus International Journal of Molecular Sciences exosome ASCs fracture nonunion osteogenesis diabetes mellitus |
title | Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus |
title_full | Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus |
title_fullStr | Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus |
title_full_unstemmed | Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus |
title_short | Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus |
title_sort | exosomes derived from adipose stem cells enhance bone fracture healing via the activation of the wnt3a β catenin signaling pathway in rats with type 2 diabetes mellitus |
topic | exosome ASCs fracture nonunion osteogenesis diabetes mellitus |
url | https://www.mdpi.com/1422-0067/24/5/4852 |
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