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Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage
BACKGROUND: We investigated two distinct synovial fibroblast populations that were located preferentially in the lining or sub-lining layers and defined by their expression of either podoplanin (PDPN) or CD248, and explored their ability to undergo self-assembly and transmigration in vivo. METHODS:...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116193/ https://www.ncbi.nlm.nih.gov/pubmed/27863512 http://dx.doi.org/10.1186/s13075-016-1156-1 |
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author | Croft, Adam P. Naylor, Amy J. Marshall, Jennifer L. Hardie, Debbie L. Zimmermann, Birgit Turner, Jason Desanti, Guillaume Adams, Holly Yemm, Adrian I. Müller-Ladner, Ulf Dayer, Jean-Michel Neumann, Elena Filer, Andrew Buckley, Christopher D. |
author_facet | Croft, Adam P. Naylor, Amy J. Marshall, Jennifer L. Hardie, Debbie L. Zimmermann, Birgit Turner, Jason Desanti, Guillaume Adams, Holly Yemm, Adrian I. Müller-Ladner, Ulf Dayer, Jean-Michel Neumann, Elena Filer, Andrew Buckley, Christopher D. |
author_sort | Croft, Adam P. |
collection | PubMed |
description | BACKGROUND: We investigated two distinct synovial fibroblast populations that were located preferentially in the lining or sub-lining layers and defined by their expression of either podoplanin (PDPN) or CD248, and explored their ability to undergo self-assembly and transmigration in vivo. METHODS: Synovial fibroblasts (SF) were cultured in vitro and phenotypic changes following stimulation with interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were examined. To examine the phenotype of SF in vivo, a severe combined immunodeficiency (SCID) human-mouse model of cartilage destruction was utilised. RESULTS: SF in the lining layer in rheumatoid arthritis (RA) expressed high levels of PDPN compared to the normal synovium, whereas CD248 expression was restricted to sub-lining layer cells. TNF-α or IL1 stimulation in vitro resulted in an increased expression of PDPN. In contrast, stimulation with TGF-β1 induced CD248 expression. In the SCID human-mouse model, rheumatoid SF recapitulated the expression of PDPN and CD248. Fibroblasts adjacent to cartilage expressed PDPN, and attached to, invaded, and degraded cartilage. PDPN(+) CD248(–) SF preceded the appearance of PDPN(–) CD248(+) cells in contralateral implants. CONCLUSIONS: We have identified two distinct SF populations identified by expression of either PDPN or CD248 which are located within different anatomical compartments of the inflamed synovial membrane. These markers discriminate between SF subsets with distinct biological properties. As PDPN-expressing cells are associated with early fibroblast migration and cartilage erosion in vivo, we propose that PDPN-expressing cells may be an attractive therapeutic target in RA. |
format | Online Article Text |
id | pubmed-5116193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-51161932016-11-25 Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage Croft, Adam P. Naylor, Amy J. Marshall, Jennifer L. Hardie, Debbie L. Zimmermann, Birgit Turner, Jason Desanti, Guillaume Adams, Holly Yemm, Adrian I. Müller-Ladner, Ulf Dayer, Jean-Michel Neumann, Elena Filer, Andrew Buckley, Christopher D. Arthritis Res Ther Research Article BACKGROUND: We investigated two distinct synovial fibroblast populations that were located preferentially in the lining or sub-lining layers and defined by their expression of either podoplanin (PDPN) or CD248, and explored their ability to undergo self-assembly and transmigration in vivo. METHODS: Synovial fibroblasts (SF) were cultured in vitro and phenotypic changes following stimulation with interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were examined. To examine the phenotype of SF in vivo, a severe combined immunodeficiency (SCID) human-mouse model of cartilage destruction was utilised. RESULTS: SF in the lining layer in rheumatoid arthritis (RA) expressed high levels of PDPN compared to the normal synovium, whereas CD248 expression was restricted to sub-lining layer cells. TNF-α or IL1 stimulation in vitro resulted in an increased expression of PDPN. In contrast, stimulation with TGF-β1 induced CD248 expression. In the SCID human-mouse model, rheumatoid SF recapitulated the expression of PDPN and CD248. Fibroblasts adjacent to cartilage expressed PDPN, and attached to, invaded, and degraded cartilage. PDPN(+) CD248(–) SF preceded the appearance of PDPN(–) CD248(+) cells in contralateral implants. CONCLUSIONS: We have identified two distinct SF populations identified by expression of either PDPN or CD248 which are located within different anatomical compartments of the inflamed synovial membrane. These markers discriminate between SF subsets with distinct biological properties. As PDPN-expressing cells are associated with early fibroblast migration and cartilage erosion in vivo, we propose that PDPN-expressing cells may be an attractive therapeutic target in RA. BioMed Central 2016-11-18 2016 /pmc/articles/PMC5116193/ /pubmed/27863512 http://dx.doi.org/10.1186/s13075-016-1156-1 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Croft, Adam P. Naylor, Amy J. Marshall, Jennifer L. Hardie, Debbie L. Zimmermann, Birgit Turner, Jason Desanti, Guillaume Adams, Holly Yemm, Adrian I. Müller-Ladner, Ulf Dayer, Jean-Michel Neumann, Elena Filer, Andrew Buckley, Christopher D. Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage |
title | Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage |
title_full | Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage |
title_fullStr | Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage |
title_full_unstemmed | Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage |
title_short | Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage |
title_sort | rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116193/ https://www.ncbi.nlm.nih.gov/pubmed/27863512 http://dx.doi.org/10.1186/s13075-016-1156-1 |
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