Journal article
Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.3MB, Terms of use)
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- Publisher copy:
- 10.1186/s13075-016-1156-1
Authors
- Publisher:
- BioMed Central
- Journal:
- Arthritis Research and Therapy More from this journal
- Volume:
- 18
- Issue:
- 1
- Pages:
- 270
- Publication date:
- 2016-11-18
- Acceptance date:
- 2016-10-19
- DOI:
- EISSN:
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1478-6362
- ISSN:
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1478-6354
- Pubs id:
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pubs:727905
- UUID:
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uuid:fa8ad3a3-79fe-4623-8323-4bb04ce107d7
- Local pid:
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pubs:727905
- Source identifiers:
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727905
- Deposit date:
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2018-05-15
Terms of use
- Copyright holder:
- Buckley et al
- Copyright date:
- 2016
- Notes:
- © The Author(s). 2016 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.
- Licence:
- CC Attribution (CC BY)
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