Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway

Osteoporosis is the most common bone metabolic disease. Emerging evidence suggests that exosomes are secreted by diverse cells such as bone marrow mesenchymal stem cells (BMSCs), and play important role in cell-to-cell communication and tissue homeostasis. Recently, the discovery of exosomes has att...

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Autores principales: Zhi Peng, Sheng Lu, Zhenkai Lou, Zhongjie Li, Shaobo Li, Kaishun Yang, Chao Li
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Publicado: Taylor & Francis Group 2021
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spelling oai:doaj.org-article:a5a500cf3407448f81c35503383989eb2021-11-04T15:51:54ZExosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway2165-59792165-598710.1080/21655979.2021.1996015https://doaj.org/article/a5a500cf3407448f81c35503383989eb2021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1996015https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Osteoporosis is the most common bone metabolic disease. Emerging evidence suggests that exosomes are secreted by diverse cells such as bone marrow mesenchymal stem cells (BMSCs), and play important role in cell-to-cell communication and tissue homeostasis. Recently, the discovery of exosomes has attracted attention in the field of bone remodeling. In this study, the exosomes were extracted from BMSCs and labeled by PKH-67, and then co-cultured with HFOB1.19 cells to investigate the miR-196a function on the osteoblast differentiation of HFOB1.19. The osteoblast differentiation was detected via alizarin red staining and the expression of osteoblast genes were detected by western blotting. The cell apoptosis was detected by flow cytometer. The target relationship of miR-196a and Dickkopf-1 (Dkk1) were verified by luciferase assay and western blotting. Here, we demonstrated that exosomes extracted from BMSCs (BMSC-exo) significantly promoted HFOB1.19 differentiation to osteoblasts. We found that BMSC-exo were enriched with miR-196a and delivered miR-196a to HFOB1.19 cells to inhibit its target Dkk1, which is a negative regulator of Wnt/β-catenin pathway. BMSC-exo activated Wnt/β-catenin pathway to promote osteogenic differentiation, while BMSC-exo failed to exert the effects when miR-196a was deprived. In conclusion, miR-196a delivered by exosomes from BMSCs plays an essential role in enhancing osteoblastic differentiation by targeting Dkk1 to activate Wnt/β-catenin pathway.Zhi PengSheng LuZhenkai LouZhongjie LiShaobo LiKaishun YangChao LiTaylor & Francis Grouparticleexosomesbone marrow mesenchymal stem cellsosteogenic differentiationosteoporosismicrorna-196adkk1BiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution DOAJ
collection DOAJ
language EN
topic exosomes
bone marrow mesenchymal stem cells
osteogenic differentiation
osteoporosis
microrna-196a
dkk1
Biotechnology
TP248.13-248.65
spellingShingle exosomes
bone marrow mesenchymal stem cells
osteogenic differentiation
osteoporosis
microrna-196a
dkk1
Biotechnology
TP248.13-248.65
Zhi Peng
Sheng Lu
Zhenkai Lou
Zhongjie Li
Shaobo Li
Kaishun Yang
Chao Li
Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway
description Osteoporosis is the most common bone metabolic disease. Emerging evidence suggests that exosomes are secreted by diverse cells such as bone marrow mesenchymal stem cells (BMSCs), and play important role in cell-to-cell communication and tissue homeostasis. Recently, the discovery of exosomes has attracted attention in the field of bone remodeling. In this study, the exosomes were extracted from BMSCs and labeled by PKH-67, and then co-cultured with HFOB1.19 cells to investigate the miR-196a function on the osteoblast differentiation of HFOB1.19. The osteoblast differentiation was detected via alizarin red staining and the expression of osteoblast genes were detected by western blotting. The cell apoptosis was detected by flow cytometer. The target relationship of miR-196a and Dickkopf-1 (Dkk1) were verified by luciferase assay and western blotting. Here, we demonstrated that exosomes extracted from BMSCs (BMSC-exo) significantly promoted HFOB1.19 differentiation to osteoblasts. We found that BMSC-exo were enriched with miR-196a and delivered miR-196a to HFOB1.19 cells to inhibit its target Dkk1, which is a negative regulator of Wnt/β-catenin pathway. BMSC-exo activated Wnt/β-catenin pathway to promote osteogenic differentiation, while BMSC-exo failed to exert the effects when miR-196a was deprived. In conclusion, miR-196a delivered by exosomes from BMSCs plays an essential role in enhancing osteoblastic differentiation by targeting Dkk1 to activate Wnt/β-catenin pathway.
format article
author Zhi Peng
Sheng Lu
Zhenkai Lou
Zhongjie Li
Shaobo Li
Kaishun Yang
Chao Li
author_facet Zhi Peng
Sheng Lu
Zhenkai Lou
Zhongjie Li
Shaobo Li
Kaishun Yang
Chao Li
author_sort Zhi Peng
title Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway
title_short Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway
title_full Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway
title_fullStr Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway
title_full_unstemmed Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dickkopf-1 to activate Wnt/β-catenin pathway
title_sort exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering mir-196a that targeted dickkopf-1 to activate wnt/β-catenin pathway
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/a5a500cf3407448f81c35503383989eb
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AT shenglu exosomesfrombonemarrowmesenchymalstemcellspromotedosteogenicdifferentiationbydeliveringmir196athattargeteddickkopf1toactivatewntbcateninpathway
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AT shaoboli exosomesfrombonemarrowmesenchymalstemcellspromotedosteogenicdifferentiationbydeliveringmir196athattargeteddickkopf1toactivatewntbcateninpathway
AT kaishunyang exosomesfrombonemarrowmesenchymalstemcellspromotedosteogenicdifferentiationbydeliveringmir196athattargeteddickkopf1toactivatewntbcateninpathway
AT chaoli exosomesfrombonemarrowmesenchymalstemcellspromotedosteogenicdifferentiationbydeliveringmir196athattargeteddickkopf1toactivatewntbcateninpathway
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