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...

Full description

Bibliographic Details
Main Authors: Dong Zhang, Weidong Xiao, Changjiang Liu, Zheng Wang, Yuhang Liu, Yifeng Yu, Chao Jian, Aixi Yu
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/5/4852
_version_ 1797615080816246784
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.
first_indexed 2024-03-11T07:21:25Z
format Article
id doaj.art-45c5ebfbc03e43489fca4364f3c3a623
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-11T07:21:25Z
publishDate 2023-03-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
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
work_keys_str_mv AT dongzhang exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus
AT weidongxiao exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus
AT changjiangliu exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus
AT zhengwang exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus
AT yuhangliu exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus
AT yifengyu exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus
AT chaojian exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus
AT aixiyu exosomesderivedfromadiposestemcellsenhancebonefracturehealingviatheactivationofthewnt3abcateninsignalingpathwayinratswithtype2diabetesmellitus