miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis

miRNAs are broad participants in vertebrate biological processes, and they are also the major players in pathological processes. miR-125a-5p was recently found a modulator in the progression of osteoarthritis (OA). Our study was aimed to explore the role and underlying mechanisms of miR-125a-5p-abun...

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Autores principales:	Qingqing Xia, Quan Wang, Jie Li, Junjuan Wang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	traumatic osteoarthritis chondrocyte degeneration bone marrow mesenchymal stem cells exosomes mir-125a-5p e2f2 Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/58a8b92c5bd645379fc3c4a2971968ef
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spelling	oai:doaj.org-article:58a8b92c5bd645379fc3c4a2971968ef2021-11-04T15:51:54ZmiR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis2165-59792165-598710.1080/21655979.2021.1995580https://doaj.org/article/58a8b92c5bd645379fc3c4a2971968ef2021-10-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1995580https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987miRNAs are broad participants in vertebrate biological processes, and they are also the major players in pathological processes. miR-125a-5p was recently found a modulator in the progression of osteoarthritis (OA). Our study was aimed to explore the role and underlying mechanisms of miR-125a-5p-abundant exosomes derived from mesenchymal stem cells (MSC) on OA progression. We separated bone marrow mesenchymal stem cells (BMSCs) as well as the exosomes from traumatic OA patients. The immunofluorescence and cartilage staining were implemented for the observation and the assessment on endocytosis of chondrocytes and exosomal miR-125a-5p efficacy to cartilage degradation. Dual luciferase reporter assay was performed to verified the relationship between miR-125a-5p and E2F2. Then, the function of exosomal miR-125a-5p were examined on chondrocyte degeneration in vitro and in vivo. Our findings indicated that E2F2 expression was elevated while the miR-125a-5p was down in traumatic OA cartilage tissue, showing a negative correlation of the former and the latter. miR-125a-5p targets E2F2 in traumatic OA cartilage tissue and leads to the down-expression of E2F2. The E2F2 expression in chondrocytes was decreased after internalization of exosomes. We additionally found that BMSCs-derived exosomes were rich in miR-125a-5p content and chondrocytes can have it internalized. miR-125a-5p is endowed with a trait of accelerating chondrocytes migration, which is going along with the up-expressions of Collagen II, aggrecan and SOX9 and the down-expression of MMP-13 in vitro. Besides that, the mice model with post-traumatic OA turned out that exosomal miR-125a-5p might beget an alleviation in chondrocyte extracellular matrix degradation. All these outcomes revealed that BMSCs-derived exosomal miR-125a-5p is a positive regulator for chondrocyte migration and inhibit cartilage degeneration We thus were reasonable to believe that transferring of exosomal miR-125a-5p is a prospective strategy for OA treatment.Qingqing XiaQuan WangJie LiJunjuan WangTaylor & Francis Grouparticletraumatic osteoarthritischondrocyte degenerationbone marrow mesenchymal stem cellsexosomesmir-125a-5pe2f2BiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	traumatic osteoarthritis chondrocyte degeneration bone marrow mesenchymal stem cells exosomes mir-125a-5p e2f2 Biotechnology TP248.13-248.65
spellingShingle	traumatic osteoarthritis chondrocyte degeneration bone marrow mesenchymal stem cells exosomes mir-125a-5p e2f2 Biotechnology TP248.13-248.65 Qingqing Xia Quan Wang Jie Li Junjuan Wang miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis
description	miRNAs are broad participants in vertebrate biological processes, and they are also the major players in pathological processes. miR-125a-5p was recently found a modulator in the progression of osteoarthritis (OA). Our study was aimed to explore the role and underlying mechanisms of miR-125a-5p-abundant exosomes derived from mesenchymal stem cells (MSC) on OA progression. We separated bone marrow mesenchymal stem cells (BMSCs) as well as the exosomes from traumatic OA patients. The immunofluorescence and cartilage staining were implemented for the observation and the assessment on endocytosis of chondrocytes and exosomal miR-125a-5p efficacy to cartilage degradation. Dual luciferase reporter assay was performed to verified the relationship between miR-125a-5p and E2F2. Then, the function of exosomal miR-125a-5p were examined on chondrocyte degeneration in vitro and in vivo. Our findings indicated that E2F2 expression was elevated while the miR-125a-5p was down in traumatic OA cartilage tissue, showing a negative correlation of the former and the latter. miR-125a-5p targets E2F2 in traumatic OA cartilage tissue and leads to the down-expression of E2F2. The E2F2 expression in chondrocytes was decreased after internalization of exosomes. We additionally found that BMSCs-derived exosomes were rich in miR-125a-5p content and chondrocytes can have it internalized. miR-125a-5p is endowed with a trait of accelerating chondrocytes migration, which is going along with the up-expressions of Collagen II, aggrecan and SOX9 and the down-expression of MMP-13 in vitro. Besides that, the mice model with post-traumatic OA turned out that exosomal miR-125a-5p might beget an alleviation in chondrocyte extracellular matrix degradation. All these outcomes revealed that BMSCs-derived exosomal miR-125a-5p is a positive regulator for chondrocyte migration and inhibit cartilage degeneration We thus were reasonable to believe that transferring of exosomal miR-125a-5p is a prospective strategy for OA treatment.
format	article
author	Qingqing Xia Quan Wang Jie Li Junjuan Wang
author_facet	Qingqing Xia Quan Wang Jie Li Junjuan Wang
author_sort	Qingqing Xia
title	miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis
title_short	miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis
title_full	miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis
title_fullStr	miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis
title_full_unstemmed	miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis
title_sort	mir-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting e2f2 in traumatic osteoarthritis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/58a8b92c5bd645379fc3c4a2971968ef
work_keys_str_mv	AT qingqingxia mir125a5pabundantexosomesderivedfrommesenchymalstemcellssuppresschondrocytedegenerationviatargetinge2f2intraumaticosteoarthritis AT quanwang mir125a5pabundantexosomesderivedfrommesenchymalstemcellssuppresschondrocytedegenerationviatargetinge2f2intraumaticosteoarthritis AT jieli mir125a5pabundantexosomesderivedfrommesenchymalstemcellssuppresschondrocytedegenerationviatargetinge2f2intraumaticosteoarthritis AT junjuanwang mir125a5pabundantexosomesderivedfrommesenchymalstemcellssuppresschondrocytedegenerationviatargetinge2f2intraumaticosteoarthritis
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miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis

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