The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation

Abstract The differentiation of osteoblasts is under complex regulation that includes autocrine and paracrine signaling from MSCs. Exosomes are important components of the MSC secretome and their cargo contains numerous miRNAs. In this study, the importance of MSC miRNAs in modulation of osteoblasti...

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Autores principales:	Sajjad Shirazi, Chun-Chieh Huang, Miya Kang, Yu Lu, Sriram Ravindran, Lyndon F. Cooper
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c35d2183caae4a4890e829a74ab688ab
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spelling	oai:doaj.org-article:c35d2183caae4a4890e829a74ab688ab2021-12-02T13:17:55ZThe importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation10.1038/s41598-021-85306-22045-2322https://doaj.org/article/c35d2183caae4a4890e829a74ab688ab2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85306-2https://doaj.org/toc/2045-2322Abstract The differentiation of osteoblasts is under complex regulation that includes autocrine and paracrine signaling from MSCs. Exosomes are important components of the MSC secretome and their cargo contains numerous miRNAs. In this study, the importance of MSC miRNAs in modulation of osteoblastic differentiation was examined by global reduction of miRNA biosynthesis in Dicer knock down hMSCs. We additionally impaired hMSC responses to miRNAs by knockdown of Argonaute 2 expression. Knockdown of Dicer and Argonaute 2 both reduced osteoblastic differentiation of hMSCs. This was observed at the levels of hMSC culture mineralization and osteoblastic gene expression. The treatment of Dicer deficient hMSCs with wild type hMSC exosomes effectively recovered the impaired osteoblastic differentiation. Dicer knockdown reduced the quantity and diversity of miRNAs present in hMSC exosomes. miRSeq data and KEGG analysis implicated the miRNA-dependent effects on multiple osteoinductive pathways in Dicer deficient cells, including the Hippo signaling and TGF-beta signaling pathways. Treatment of hMSCs with mimics of miRNAs significantly downregulated in Dicer knockdown cells recovered functions of exosome-mediated signaling in hMSCs. These results indicate that hMSC exosomes exert miRNA-dependent control that contributes to osteoblastic differentiation.Sajjad ShiraziChun-Chieh HuangMiya KangYu LuSriram RavindranLyndon F. CooperNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sajjad Shirazi Chun-Chieh Huang Miya Kang Yu Lu Sriram Ravindran Lyndon F. Cooper The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation
description	Abstract The differentiation of osteoblasts is under complex regulation that includes autocrine and paracrine signaling from MSCs. Exosomes are important components of the MSC secretome and their cargo contains numerous miRNAs. In this study, the importance of MSC miRNAs in modulation of osteoblastic differentiation was examined by global reduction of miRNA biosynthesis in Dicer knock down hMSCs. We additionally impaired hMSC responses to miRNAs by knockdown of Argonaute 2 expression. Knockdown of Dicer and Argonaute 2 both reduced osteoblastic differentiation of hMSCs. This was observed at the levels of hMSC culture mineralization and osteoblastic gene expression. The treatment of Dicer deficient hMSCs with wild type hMSC exosomes effectively recovered the impaired osteoblastic differentiation. Dicer knockdown reduced the quantity and diversity of miRNAs present in hMSC exosomes. miRSeq data and KEGG analysis implicated the miRNA-dependent effects on multiple osteoinductive pathways in Dicer deficient cells, including the Hippo signaling and TGF-beta signaling pathways. Treatment of hMSCs with mimics of miRNAs significantly downregulated in Dicer knockdown cells recovered functions of exosome-mediated signaling in hMSCs. These results indicate that hMSC exosomes exert miRNA-dependent control that contributes to osteoblastic differentiation.
format	article
author	Sajjad Shirazi Chun-Chieh Huang Miya Kang Yu Lu Sriram Ravindran Lyndon F. Cooper
author_facet	Sajjad Shirazi Chun-Chieh Huang Miya Kang Yu Lu Sriram Ravindran Lyndon F. Cooper
author_sort	Sajjad Shirazi
title	The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation
title_short	The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation
title_full	The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation
title_fullStr	The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation
title_full_unstemmed	The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation
title_sort	importance of cellular and exosomal mirnas in mesenchymal stem cell osteoblastic differentiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c35d2183caae4a4890e829a74ab688ab
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The importance of cellular and exosomal miRNAs in mesenchymal stem cell osteoblastic differentiation

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