BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic rats

Diabetic patients often face poor repair of bone defects, which may be related to the reduced osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs) and the polarization of M1/M2 macrophage imbalance leading to an inflammatory response. The ability of BMSC-derived exosomes (BMSC-Exos) and...

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Main Authors: Yilin He, Yihu Wang, Shujia Yu, Lingxiao Wang, Yiping Dou, Ruihong Ma, Shiyu Cao, Wenpeng Song, Pan Ma
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Materials & Design
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Online Access:http://www.sciencedirect.com/science/article/pii/S026412752400892X
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author Yilin He
Yihu Wang
Shujia Yu
Lingxiao Wang
Yiping Dou
Ruihong Ma
Shiyu Cao
Wenpeng Song
Pan Ma
author_facet Yilin He
Yihu Wang
Shujia Yu
Lingxiao Wang
Yiping Dou
Ruihong Ma
Shiyu Cao
Wenpeng Song
Pan Ma
author_sort Yilin He
collection DOAJ
description Diabetic patients often face poor repair of bone defects, which may be related to the reduced osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs) and the polarization of M1/M2 macrophage imbalance leading to an inflammatory response. The ability of BMSC-derived exosomes (BMSC-Exos) and BMP2 to exert both bone tissue regeneration and immunomodulation is expected to resolve this clinical dilemma. In this study, we demonstrate that exosomes derived from BMP2-treated BMSCs (BMP2-Exos) in a diabetic microenvironment exhibit enhanced osteogenic effects. Additionally, compared to the blank control group, macrophages stimulated by BMP2-Exos were more polarized towards the M2 type. These results were verified in vivo by GelMA loaded exosomes in the diabetic rat skull defect model. Importantly, we found that BMP2-Exos can upregulate the PI3K/AKT signaling pathway in diabetic BMSCs and improved osteogenic function and M2 macrophage polarization in diabetes-impaired BMSC-Exos in vitro. In conclusion, the present study revealed that BMP2 pretreatment can enhance the ability of BMSC-Exos to promote osteogenesis in diabetic bone defect areas, provides a preliminary exploration of the underlying mechanisms. Our study provided important experimental basis and innovative ideas for the application of exosomes therapy in the field of bone tissue regeneration.
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issn 0264-1275
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spelling doaj-art-25c8f3963d584bc2abdcc08e8041aacb2025-08-20T02:52:35ZengElsevierMaterials & Design0264-12752024-12-0124811351710.1016/j.matdes.2024.113517BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic ratsYilin He0Yihu Wang1Shujia Yu2Lingxiao Wang3Yiping Dou4Ruihong Ma5Shiyu Cao6Wenpeng Song7Pan Ma8Implant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing 100050, ChinaKey Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaImplant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing 100050, ChinaImplant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing 100050, ChinaImplant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing 100050, ChinaImplant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing 100050, ChinaImplant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing 100050, ChinaDepartment of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, ChinaImplant Department, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tiantan Xili No.4, Dongcheng District, Beijing 100050, China; Corresponding author.Diabetic patients often face poor repair of bone defects, which may be related to the reduced osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs) and the polarization of M1/M2 macrophage imbalance leading to an inflammatory response. The ability of BMSC-derived exosomes (BMSC-Exos) and BMP2 to exert both bone tissue regeneration and immunomodulation is expected to resolve this clinical dilemma. In this study, we demonstrate that exosomes derived from BMP2-treated BMSCs (BMP2-Exos) in a diabetic microenvironment exhibit enhanced osteogenic effects. Additionally, compared to the blank control group, macrophages stimulated by BMP2-Exos were more polarized towards the M2 type. These results were verified in vivo by GelMA loaded exosomes in the diabetic rat skull defect model. Importantly, we found that BMP2-Exos can upregulate the PI3K/AKT signaling pathway in diabetic BMSCs and improved osteogenic function and M2 macrophage polarization in diabetes-impaired BMSC-Exos in vitro. In conclusion, the present study revealed that BMP2 pretreatment can enhance the ability of BMSC-Exos to promote osteogenesis in diabetic bone defect areas, provides a preliminary exploration of the underlying mechanisms. Our study provided important experimental basis and innovative ideas for the application of exosomes therapy in the field of bone tissue regeneration.http://www.sciencedirect.com/science/article/pii/S026412752400892XBone morphogenetic protein 2Bone regenerationDiabetesBone marrow mesenchymal stem cellsExosomesPI3K/AKT signaling pathway
spellingShingle Yilin He
Yihu Wang
Shujia Yu
Lingxiao Wang
Yiping Dou
Ruihong Ma
Shiyu Cao
Wenpeng Song
Pan Ma
BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic rats
Materials & Design
Bone morphogenetic protein 2
Bone regeneration
Diabetes
Bone marrow mesenchymal stem cells
Exosomes
PI3K/AKT signaling pathway
title BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic rats
title_full BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic rats
title_fullStr BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic rats
title_full_unstemmed BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic rats
title_short BMP2 enhance the osteogenic effect of BMSCs-derived exosomes in skull defect of diabetic rats
title_sort bmp2 enhance the osteogenic effect of bmscs derived exosomes in skull defect of diabetic rats
topic Bone morphogenetic protein 2
Bone regeneration
Diabetes
Bone marrow mesenchymal stem cells
Exosomes
PI3K/AKT signaling pathway
url http://www.sciencedirect.com/science/article/pii/S026412752400892X
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