M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells

Abstract Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the...

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Main Authors: Zhang Bin-bin, Zha Xi Da-wa, Li Chao, Zhang Lan-tao, Wu Tao, Lu Chuan, Liu Chao-zheng, Li De-chun, Feng Chang, Wei Shu-qing, Dong Zu-nan, Pei Xian-wei, Zhi-xia Zhang, Li Ke-wen
Format: Article
Language:English
Published: BMC 2022-03-01
Series:Journal of Orthopaedic Surgery and Research
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Online Access:https://doi.org/10.1186/s13018-022-03029-0
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author Zhang Bin-bin
Zha Xi Da-wa
Li Chao
Zhang Lan-tao
Wu Tao
Lu Chuan
Liu Chao-zheng
Li De-chun
Feng Chang
Wei Shu-qing
Dong Zu-nan
Pei Xian-wei
Zhi-xia Zhang
Li Ke-wen
author_facet Zhang Bin-bin
Zha Xi Da-wa
Li Chao
Zhang Lan-tao
Wu Tao
Lu Chuan
Liu Chao-zheng
Li De-chun
Feng Chang
Wei Shu-qing
Dong Zu-nan
Pei Xian-wei
Zhi-xia Zhang
Li Ke-wen
author_sort Zhang Bin-bin
collection DOAJ
description Abstract Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public. Methods M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins. Results The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation. Conclusions The present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.
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spelling doaj.art-67ab5a115c5646a7be382a1fb54701bd2022-12-22T04:23:32ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2022-03-0117111010.1186/s13018-022-03029-0M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cellsZhang Bin-bin0Zha Xi Da-wa1Li Chao2Zhang Lan-tao3Wu Tao4Lu Chuan5Liu Chao-zheng6Li De-chun7Feng Chang8Wei Shu-qing9Dong Zu-nan10Pei Xian-wei11Zhi-xia Zhang12Li Ke-wen13Department of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalDepartment of Joint Surgery, Qinghai University Affiliated HospitalState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Out-Patient, School of Stomatology, Fourth Military Medical UniversityDepartment of Joint Surgery, Qinghai University Affiliated HospitalAbstract Background Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public. Methods M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins. Results The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation. Conclusions The present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.https://doi.org/10.1186/s13018-022-03029-0ExosomesmiRNA-26a-5pMacrophagesOsteogenic differentiation
spellingShingle Zhang Bin-bin
Zha Xi Da-wa
Li Chao
Zhang Lan-tao
Wu Tao
Lu Chuan
Liu Chao-zheng
Li De-chun
Feng Chang
Wei Shu-qing
Dong Zu-nan
Pei Xian-wei
Zhi-xia Zhang
Li Ke-wen
M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells
Journal of Orthopaedic Surgery and Research
Exosomes
miRNA-26a-5p
Macrophages
Osteogenic differentiation
title M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells
title_full M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells
title_fullStr M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells
title_full_unstemmed M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells
title_short M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells
title_sort m2 macrophagy derived exosomal mirna 26a 5p induces osteogenic differentiation of bone mesenchymal stem cells
topic Exosomes
miRNA-26a-5p
Macrophages
Osteogenic differentiation
url https://doi.org/10.1186/s13018-022-03029-0
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