Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo

Abstract Rheumatoid arthritis (RA) is a debilitating and painful inflammatory autoimmune disease characterised by the accumulation of leukocytes in the synovium, cartilage destruction and bone erosion. The immunomodulatory effects of bone marrow derived mesenchymal stem cells (MSCs) has been widely...

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Autores principales:	Fiona K. Jones, Andrei Stefan, Alasdair G. Kay, Mairead Hyland, Rebecca Morgan, Nicholas R. Forsyth, Addolorata Pisconti, Oksana Kehoe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e3998836d8ca4d74978551ff08824914
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spelling	oai:doaj.org-article:e3998836d8ca4d74978551ff088249142021-12-02T11:40:49ZSyndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo10.1038/s41598-020-77514-z2045-2322https://doaj.org/article/e3998836d8ca4d74978551ff088249142020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77514-zhttps://doaj.org/toc/2045-2322Abstract Rheumatoid arthritis (RA) is a debilitating and painful inflammatory autoimmune disease characterised by the accumulation of leukocytes in the synovium, cartilage destruction and bone erosion. The immunomodulatory effects of bone marrow derived mesenchymal stem cells (MSCs) has been widely studied and the recent observations that syndecan-3 (SDC3) is selectively pro-inflammatory in the joint led us to hypothesise that SDC3 might play an important role in MSC biology. MSCs isolated from bone marrow of wild type and Sdc3−/− mice were used to assess immunophenotype, differentiation, adhesion and migration properties and cell signalling pathways. While both cell types show similar differentiation potential and forward scatter values, the cell complexity in wild type MSCs was significantly higher than in Sdc3−/− cells and was accompanied by lower spread surface area. Moreover, Sdc3−/− MSCs adhered more rapidly to collagen type I and showed a dramatic increase in AKT phosphorylation, accompanied by a decrease in ERK1/2 phosphorylation compared with control cells. In a mouse model of antigen-induced inflammatory arthritis, intraarticular injection of Sdc3−/− MSCs yielded enhanced efficacy compared to injection of wild type MSCs. In conclusion, our data suggest that syndecan-3 regulates MSC adhesion and efficacy in inflammatory arthritis, likely via induction of the AKT pathway.Fiona K. JonesAndrei StefanAlasdair G. KayMairead HylandRebecca MorganNicholas R. ForsythAddolorata PiscontiOksana KehoeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fiona K. Jones Andrei Stefan Alasdair G. Kay Mairead Hyland Rebecca Morgan Nicholas R. Forsyth Addolorata Pisconti Oksana Kehoe Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo
description	Abstract Rheumatoid arthritis (RA) is a debilitating and painful inflammatory autoimmune disease characterised by the accumulation of leukocytes in the synovium, cartilage destruction and bone erosion. The immunomodulatory effects of bone marrow derived mesenchymal stem cells (MSCs) has been widely studied and the recent observations that syndecan-3 (SDC3) is selectively pro-inflammatory in the joint led us to hypothesise that SDC3 might play an important role in MSC biology. MSCs isolated from bone marrow of wild type and Sdc3−/− mice were used to assess immunophenotype, differentiation, adhesion and migration properties and cell signalling pathways. While both cell types show similar differentiation potential and forward scatter values, the cell complexity in wild type MSCs was significantly higher than in Sdc3−/− cells and was accompanied by lower spread surface area. Moreover, Sdc3−/− MSCs adhered more rapidly to collagen type I and showed a dramatic increase in AKT phosphorylation, accompanied by a decrease in ERK1/2 phosphorylation compared with control cells. In a mouse model of antigen-induced inflammatory arthritis, intraarticular injection of Sdc3−/− MSCs yielded enhanced efficacy compared to injection of wild type MSCs. In conclusion, our data suggest that syndecan-3 regulates MSC adhesion and efficacy in inflammatory arthritis, likely via induction of the AKT pathway.
format	article
author	Fiona K. Jones Andrei Stefan Alasdair G. Kay Mairead Hyland Rebecca Morgan Nicholas R. Forsyth Addolorata Pisconti Oksana Kehoe
author_facet	Fiona K. Jones Andrei Stefan Alasdair G. Kay Mairead Hyland Rebecca Morgan Nicholas R. Forsyth Addolorata Pisconti Oksana Kehoe
author_sort	Fiona K. Jones
title	Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo
title_short	Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo
title_full	Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo
title_fullStr	Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo
title_full_unstemmed	Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo
title_sort	syndecan-3 regulates msc adhesion, erk and akt signalling in vitro and its deletion enhances msc efficacy in a model of inflammatory arthritis in vivo
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e3998836d8ca4d74978551ff08824914
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Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo

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