Exosomal miR-335 derived from mature dendritic cells enhanced mesenchymal stem cell-mediated bone regeneration of bone defects in athymic rats

Cao, Zhong-Liu; Wu, Yanfeng; Liu, Yü; Zou, Lingfeng; Liu, Yang; Lin, Sijian; Wang, Jue; Yuan, Zhen; Dai, Jianghua

doi:10.1186/s10020-021-00268-5

Cited by 29 publications

(19 citation statements)

References 30 publications

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“…Because of the signals and nutrients delivered by exosomes, macrophages are broadly involved in a number of physiological processes and pathological diseases such as cancer [ 18 ], inflammation [ 19 ] and tissue repair [ 20 ]. In addition, macrophages exosomes also participate in bone remodeling [ 21 ]. However, the exosomes derived from different types of macrophages have been shown to exert different functional effects on osteogenesis [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA

et al. 2022

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Background Periodontitis is characterized by progressive inflammation and alveolar bone loss resulting in tooth loss finally. Macrophages including pro-inflammatory M1-like macrophages and reparative M2-like macrophages play a vital role in inflammation and tissue homeostasis in periodontitis. Among them, reparative M2-like macrophages have been shown to promote tissue repair and prevent bone loss. However, the mechanism of reparative M2 macrophages-induced osteoprotective effect remains elusive. Results Exosomes from reparative M2-like macrophages (M2-Exos) were isolated and identified successfully. M2-Exos could promote bone marrow stromal cells (BMSCs) osteogenic differentiation while suppressing bone marrow derived macrophage (BMDM) osteoclast formation, and prohibit pathological alveolar bone resorption because of the intercellular communication via exosomes. High expression level of IL-10 mRNA was detected not only in reparative M2-like macrophages but also in M2-Exos. Meanwhile, IL-10 expression level in BMSCs or BMDM was also upregulated significantly after co-culturing with M2-Exos in a concentration-dependent manner. In vitro, recombinant IL-10 proteins had the ability to selectively promote osteogenic differentiation of BMSCs and hinder osteoclast differentiation of BMDM. Moreover, after treatment with M2-Exos and IL-10R antibody together, the capacity of promoting osteogenesis and suppressing osteoclastogenesis of M2-Exos was significantly reversed. In vivo experiments further showed that M2-Exos reduced alveolar bone resorption in mice with periodontitis via IL-10/IL-10R pathway. Conclusion In conclusion, our results demonstrate that the reparative M2-like macrophages could promote osteogenesis while inhibiting osteoclastogenesis in vitro as well as protect alveolar bone against resorption in vivo significantly. M2-Exos could upregulate the IL-10 cytokines expression of BMSCs and BMDM via delivering exosomal IL-10 mRNA to cells directly, leading to activation of the cellular IL-10/IL-10R pathway to regulate cells differentiation and bone metabolism. These results might partly account for the mechanism of osteoprotective effect of reparative M2-like macrophages and provide a novel perspective and a potential therapeutic approach on improving alveolar resorption by M2-Exos. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA

et al. 2022

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“…Recent studies have found that exosomes play a vital role in bone diseases ( 15 , 16 ). In a rat calvarial defect model, macrophage exosomes could mediate bone regeneration ( 17 ). However, it has also been reported that exosomes from M0, M1, and M2 macrophages might have different effects on the osteogenic differentiation of BMSCs ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

Exosomes Derived From M2 Macrophages Facilitate Osteogenesis and Reduce Adipogenesis of BMSCs

Wang

et al. 2021

Front. Endocrinol.

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Bone regeneration is a complex process that requires the coordination of osteogenesis and osteoclastogenesis. The balance between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) plays a major role in the process of bone formation. Recently, intercellular communication between bone cells and surrounding cells has been gradually recognized, and macrophages on the surface of bone have been proven to regulate bone metabolism. However, the underlying mechanisms have not been fully elucidated. Recent studies have indicated that exosomes are vital messengers for cell-cell communication in various biological processes. In this experiment, we found that exosomes derived from M2 macrophages (M2D-Exos) could inhibit adipogenesis and promote osteogenesis of BMSCs. M2D-Exo intervention increased the expression of miR-690, IRS-1, and TAZ in BMSCs. Additionally, miR-690 knockdown in M2 macrophages with a miR-690 inhibitor partially counteracted the effect of M2D-Exos on BMSC differentiation and the upregulation of IRS-1 and TAZ expression. Taken together, the results of our study indicate that exosomes isolated from M2 macrophages could facilitate osteogenesis and reduce adipogenesis through the miR-690/IRS-1/TAZ axis and might be a therapeutic tool for bone loss diseases.

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“…For example, the RNA-sequencing of osteogenic exosomes from human MSCs suggests that exosomes include upregulated osteogenic miRNAs (Hsa-miR-146a-5p, Hsa-miR-503-5p, Hsa-miR-483-3p, and Hsa-miR-129-5p) or downregulated anti-osteogenic miRNAs (Hsa-miR-32-5p, Hsa-miR-133a-3p, and Hsa-miR-204-5p), which activate the PI3K/Akt and MAPK signaling pathways ( Zhai et al, 2020 ). In addition, MSC-released exosomal miR-1260a ( Wu et al, 2021 ); miR-335 ( Cao et al, 2021 ); miR-140 and miR-375 ( Chen et al, 2019 ); miR-26a, miR-199a, miR-21, and miR-23a-3p ( Hu et al, 2020 ); let-7a-5p, let-7c-5p, miR-328a-5p, and miR-31a-5p ( Liu A. et al, 2021 ); and miR-150-5p ( Jing et al, 2022 ) have been reported to promote osteogenesis. The exosomes promoting osteogenesis involve many pathways, such as BMP/Smad, Wnt/β-catenin, PTEN/PI3K/Akt, and Hippo signaling pathways ( Cao et al, 2021 ; Cui et al, 2016 ; Hu et al, 2020 ; Zhang et al, 2016 ).…”

Section: Applications Of Bone Engineering Scaffolds With Exosomes In ...mentioning

confidence: 99%

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

Zhang

Feng

et al. 2022

Front. Bioeng. Biotechnol.

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The treatment of bone defects is still an intractable clinical problem, despite the fact that numerous treatments are currently available. In recent decades, bone engineering scaffolds have become a promising tool to fill in the defect sites and remedy the deficiencies of bone grafts. By virtue of bone formation, vascular growth, and inflammation modulation, the combination of bone engineering scaffolds with cell-based and cell-free therapy is widely used in bone defect repair. As a key element of cell-free therapy, exosomes with bioactive molecules overcome the deficiencies of cell-based therapy and promote bone tissue regeneration via the potential of osteogenesis, angiogenesis, and inflammation modulation. Hence, this review aimed at overviewing the bone defect microenvironment and healing mechanism, summarizing current advances in bone engineering scaffolds and exosomes in bone defects to probe for future applications.

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Exosomal miR-335 derived from mature dendritic cells enhanced mesenchymal stem cell-mediated bone regeneration of bone defects in athymic rats

Cited by 29 publications

References 30 publications

Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA

Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA

Exosomes Derived From M2 Macrophages Facilitate Osteogenesis and Reduce Adipogenesis of BMSCs

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

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