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Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis
BACKGROUND: The pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Tissue repair responses include transforming growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the extracellul...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886182/ https://www.ncbi.nlm.nih.gov/pubmed/31819923 http://dx.doi.org/10.1186/s41927-019-0093-4 |
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author | Kragstrup, Tue W. Sohn, Dong H. Lepus, Christin M. Onuma, Kazuhiro Wang, Qian Robinson, William H. Sokolove, Jeremy |
author_facet | Kragstrup, Tue W. Sohn, Dong H. Lepus, Christin M. Onuma, Kazuhiro Wang, Qian Robinson, William H. Sokolove, Jeremy |
author_sort | Kragstrup, Tue W. |
collection | PubMed |
description | BACKGROUND: The pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Tissue repair responses include transforming growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the extracellular matrix, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Fibronectin containing the ED-A domain is currently being used as drug delivery target in the development of anti-inflammatory drugs (e.g. Dekavil). METHODS: In this study, samples of synovial membrane were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A fibronectin and the myofibroblast marker alpha smooth muscle actin (αSMA) was performed on fibroblast-like synovial cells (FLS) and synovial membranes. RAW 264.7 macrophages were incubated with recombinant ED-A fibronectin. RESULTS: The staining of ED-A fibronectin in OA FLS was increased by TGFβ but not by TNFα, lipopolysaccharide, or IL-6 (n = 3). ED-A fibronectin co-stained with the myofibroblast marker αSMA in both the OA FLS (n = 3) and in the OA synovial membranes (n = 8). ED-A fibronectin staining was associated with both number of lining layer cells (rho = 0.85 and p = 0.011) and sublining cells (rho = 0.88 and p = 0.007) in the OA synovium (n = 8), and co-distributed with TNFα (n = 5). Recombinant ED-A fibronectin increased the production of TNFα by RAW 264.7 macrophages (n = 3). CONCLUSIONS: The disease process in OA shares features with the chronic wound healing response. Our findings support utilizing ED-A fibronectin for drug delivery or therapeutic targeting to reduce pro-inflammatory responses in OA. |
format | Online Article Text |
id | pubmed-6886182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68861822019-12-09 Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis Kragstrup, Tue W. Sohn, Dong H. Lepus, Christin M. Onuma, Kazuhiro Wang, Qian Robinson, William H. Sokolove, Jeremy BMC Rheumatol Research Article BACKGROUND: The pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Tissue repair responses include transforming growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the extracellular matrix, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Fibronectin containing the ED-A domain is currently being used as drug delivery target in the development of anti-inflammatory drugs (e.g. Dekavil). METHODS: In this study, samples of synovial membrane were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A fibronectin and the myofibroblast marker alpha smooth muscle actin (αSMA) was performed on fibroblast-like synovial cells (FLS) and synovial membranes. RAW 264.7 macrophages were incubated with recombinant ED-A fibronectin. RESULTS: The staining of ED-A fibronectin in OA FLS was increased by TGFβ but not by TNFα, lipopolysaccharide, or IL-6 (n = 3). ED-A fibronectin co-stained with the myofibroblast marker αSMA in both the OA FLS (n = 3) and in the OA synovial membranes (n = 8). ED-A fibronectin staining was associated with both number of lining layer cells (rho = 0.85 and p = 0.011) and sublining cells (rho = 0.88 and p = 0.007) in the OA synovium (n = 8), and co-distributed with TNFα (n = 5). Recombinant ED-A fibronectin increased the production of TNFα by RAW 264.7 macrophages (n = 3). CONCLUSIONS: The disease process in OA shares features with the chronic wound healing response. Our findings support utilizing ED-A fibronectin for drug delivery or therapeutic targeting to reduce pro-inflammatory responses in OA. BioMed Central 2019-12-02 /pmc/articles/PMC6886182/ /pubmed/31819923 http://dx.doi.org/10.1186/s41927-019-0093-4 Text en © The Author(s) 2019 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 Kragstrup, Tue W. Sohn, Dong H. Lepus, Christin M. Onuma, Kazuhiro Wang, Qian Robinson, William H. Sokolove, Jeremy Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
title | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
title_full | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
title_fullStr | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
title_full_unstemmed | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
title_short | Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis |
title_sort | fibroblast-like synovial cell production of extra domain a fibronectin associates with inflammation in osteoarthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886182/ https://www.ncbi.nlm.nih.gov/pubmed/31819923 http://dx.doi.org/10.1186/s41927-019-0093-4 |
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