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Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis

BACKGROUND: Fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) are autonomously activated to maintain inflammation and joint destruction in co-transplantation models. To elucidate inducing mechanisms involved in this altered behavior, the arthritogenic potential of FLSs...

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Autores principales: Frey, Oliver, Hückel, Marion, Gajda, Mieczyslaw, Petrow, Peter K., Bräuer, Rolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251107/
https://www.ncbi.nlm.nih.gov/pubmed/30466479
http://dx.doi.org/10.1186/s13075-018-1720-y
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author Frey, Oliver
Hückel, Marion
Gajda, Mieczyslaw
Petrow, Peter K.
Bräuer, Rolf
author_facet Frey, Oliver
Hückel, Marion
Gajda, Mieczyslaw
Petrow, Peter K.
Bräuer, Rolf
author_sort Frey, Oliver
collection PubMed
description BACKGROUND: Fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) are autonomously activated to maintain inflammation and joint destruction in co-transplantation models. To elucidate inducing mechanisms involved in this altered behavior, the arthritogenic potential of FLSs from murine antigen-induced arthritis (AIA) were investigated in a transfer model. METHODS: FLSs were isolated, expanded in vitro, and transferred into knee joint cavities of severe combined immunodeficient (SCID) mice. Their arthritogenic capacity was assessed by monitoring joint swelling and evaluation of histological parameters 70 to 100 days after transfer. RESULTS: FLSs from AIA mice were able to transfer arthritis into recipient SCID mice. FLS transfer induced a chronic arthritis with recruitment of inflammatory cells and marked cartilage destruction. Long-lasting inflammation was not required for imprinting of arthritogenicity in FLSs since cells isolated from acute arthritic joints were fully competent to transfer arthritis. We also observed arthritogenic potential in FLSs isolated from contralateral non-arthritic joints in our monoarticular arthritis model. CONCLUSIONS: We show that the transformation of FLSs into arthritogenic cells occurs early in arthritis development. This challenges current hypotheses on the role of these cells in arthritis pathogenesis and opens up the way for further mechanistic studies.
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spelling pubmed-62511072018-11-26 Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis Frey, Oliver Hückel, Marion Gajda, Mieczyslaw Petrow, Peter K. Bräuer, Rolf Arthritis Res Ther Research Article BACKGROUND: Fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) are autonomously activated to maintain inflammation and joint destruction in co-transplantation models. To elucidate inducing mechanisms involved in this altered behavior, the arthritogenic potential of FLSs from murine antigen-induced arthritis (AIA) were investigated in a transfer model. METHODS: FLSs were isolated, expanded in vitro, and transferred into knee joint cavities of severe combined immunodeficient (SCID) mice. Their arthritogenic capacity was assessed by monitoring joint swelling and evaluation of histological parameters 70 to 100 days after transfer. RESULTS: FLSs from AIA mice were able to transfer arthritis into recipient SCID mice. FLS transfer induced a chronic arthritis with recruitment of inflammatory cells and marked cartilage destruction. Long-lasting inflammation was not required for imprinting of arthritogenicity in FLSs since cells isolated from acute arthritic joints were fully competent to transfer arthritis. We also observed arthritogenic potential in FLSs isolated from contralateral non-arthritic joints in our monoarticular arthritis model. CONCLUSIONS: We show that the transformation of FLSs into arthritogenic cells occurs early in arthritis development. This challenges current hypotheses on the role of these cells in arthritis pathogenesis and opens up the way for further mechanistic studies. BioMed Central 2018-11-22 2018 /pmc/articles/PMC6251107/ /pubmed/30466479 http://dx.doi.org/10.1186/s13075-018-1720-y Text en © The Author(s). 2018 Open Access This 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
Frey, Oliver
Hückel, Marion
Gajda, Mieczyslaw
Petrow, Peter K.
Bräuer, Rolf
Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis
title Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis
title_full Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis
title_fullStr Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis
title_full_unstemmed Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis
title_short Induction of chronic destructive arthritis in SCID mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis
title_sort induction of chronic destructive arthritis in scid mice by arthritogenic fibroblast-like synoviocytes derived from mice with antigen-induced arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251107/
https://www.ncbi.nlm.nih.gov/pubmed/30466479
http://dx.doi.org/10.1186/s13075-018-1720-y
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