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The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway

BACKGROUND: Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor/stem cells (CPSCs) are a type of ste...

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Autores principales: Moqbel, Safwat Adel Abdo, Zeng, Rong, Ma, Diana, Xu, Langhai, Lin, Changjian, He, Yuzhe, Ma, Chiyuan, Xu, Kai, Ran, Jisheng, Jiang, Lifeng, Wu, Lidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951683/
https://www.ncbi.nlm.nih.gov/pubmed/35337368
http://dx.doi.org/10.1186/s13287-022-02758-7
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author Moqbel, Safwat Adel Abdo
Zeng, Rong
Ma, Diana
Xu, Langhai
Lin, Changjian
He, Yuzhe
Ma, Chiyuan
Xu, Kai
Ran, Jisheng
Jiang, Lifeng
Wu, Lidong
author_facet Moqbel, Safwat Adel Abdo
Zeng, Rong
Ma, Diana
Xu, Langhai
Lin, Changjian
He, Yuzhe
Ma, Chiyuan
Xu, Kai
Ran, Jisheng
Jiang, Lifeng
Wu, Lidong
author_sort Moqbel, Safwat Adel Abdo
collection PubMed
description BACKGROUND: Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor/stem cells (CPSCs) are a type of stem cells with the ability to self- renew and differentiate. They hold a promising future for the understanding of the progression of OA and for its treatment. Previous studies have reported the relationship between mitochondrial dynamics and mesenchymal stem cell (MSC) proliferation, differentiation and aging. Mitochondrial dynamic and morphology change during stem cell differentiation. METHODS: This study was performed to access the relationship between mitochondrial dynamics and chondrogenic differentiation of CPSCs. Mitochondrial fusion and fission levels were measured during the chondrogenic differentiation process of CPSCs. After that, we used mitochondrial fusion promoter to induce fusion in CPSCs and then the chondrogenic markers were measured. Transmission electron microscopy (TEM) and confocal microscopy were used to capture the mass and fusion status of mitochondria. Lentiviruses were used to detect the role of mitofusin 2 (Mfn2) in CPSC chondrogenic differentiation. In vivo, Mfn2 was over-expressed in sheets of rat CPSCs, which were then injected intra-articularly into the knees of rats. RESULTS: Mitochondrial fusion markers were upregulated during the chondrogenic induction process of CPSCs. The mass of mitochondria was higher in differentiated CPSC, and the fusion status was obvious relative to un-differentiated CPSC. Chondrogenesis of CPSCs was upregulated with the induction by mitochondrial fusion promoter. Mfn2 over-expression significantly increased chondrocyte-specific gene expression and reversed OA through NOTCH2 signal pathway. CONCLUSIONS: Our study demonstrated that the mitochondrial fusion promotes chondrogenesis differentiation of CPSCs. Mfn2 accelerates the chondrogenesis differentiation of CPSCs through Notch2. In vivo, Mfn2-OE in sheets of rCPSCs ameliorated OA in the rat model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02758-7.
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spelling pubmed-89516832022-03-26 The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway Moqbel, Safwat Adel Abdo Zeng, Rong Ma, Diana Xu, Langhai Lin, Changjian He, Yuzhe Ma, Chiyuan Xu, Kai Ran, Jisheng Jiang, Lifeng Wu, Lidong Stem Cell Res Ther Research BACKGROUND: Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor/stem cells (CPSCs) are a type of stem cells with the ability to self- renew and differentiate. They hold a promising future for the understanding of the progression of OA and for its treatment. Previous studies have reported the relationship between mitochondrial dynamics and mesenchymal stem cell (MSC) proliferation, differentiation and aging. Mitochondrial dynamic and morphology change during stem cell differentiation. METHODS: This study was performed to access the relationship between mitochondrial dynamics and chondrogenic differentiation of CPSCs. Mitochondrial fusion and fission levels were measured during the chondrogenic differentiation process of CPSCs. After that, we used mitochondrial fusion promoter to induce fusion in CPSCs and then the chondrogenic markers were measured. Transmission electron microscopy (TEM) and confocal microscopy were used to capture the mass and fusion status of mitochondria. Lentiviruses were used to detect the role of mitofusin 2 (Mfn2) in CPSC chondrogenic differentiation. In vivo, Mfn2 was over-expressed in sheets of rat CPSCs, which were then injected intra-articularly into the knees of rats. RESULTS: Mitochondrial fusion markers were upregulated during the chondrogenic induction process of CPSCs. The mass of mitochondria was higher in differentiated CPSC, and the fusion status was obvious relative to un-differentiated CPSC. Chondrogenesis of CPSCs was upregulated with the induction by mitochondrial fusion promoter. Mfn2 over-expression significantly increased chondrocyte-specific gene expression and reversed OA through NOTCH2 signal pathway. CONCLUSIONS: Our study demonstrated that the mitochondrial fusion promotes chondrogenesis differentiation of CPSCs. Mfn2 accelerates the chondrogenesis differentiation of CPSCs through Notch2. In vivo, Mfn2-OE in sheets of rCPSCs ameliorated OA in the rat model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02758-7. BioMed Central 2022-03-25 /pmc/articles/PMC8951683/ /pubmed/35337368 http://dx.doi.org/10.1186/s13287-022-02758-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Moqbel, Safwat Adel Abdo
Zeng, Rong
Ma, Diana
Xu, Langhai
Lin, Changjian
He, Yuzhe
Ma, Chiyuan
Xu, Kai
Ran, Jisheng
Jiang, Lifeng
Wu, Lidong
The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway
title The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway
title_full The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway
title_fullStr The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway
title_full_unstemmed The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway
title_short The effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via Notch2 signal pathway
title_sort effect of mitochondrial fusion on chondrogenic differentiation of cartilage progenitor/stem cells via notch2 signal pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951683/
https://www.ncbi.nlm.nih.gov/pubmed/35337368
http://dx.doi.org/10.1186/s13287-022-02758-7
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