Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis show the imprint of synovial tissue heterogeneity: evidence of a link between an increased myofibroblast-like phenotype and high-inflammation synovitis

Kasperkovitz, Pia V.; Timmer, Trieneke C. G.; Smeets, Tom J.; Verbeet, Nicolette L.; Tak, Paul P.; van baarsen, Lisa G. M.; Baltus, Belinda; Huizinga, Tom W. J.; Pieterman, Elsbet; Fero, Mike; Firestein, Gary S.; van der Pouw Kraan, Tineke C. T. M.; Verweij, Cornelis L.

doi:10.1002/art.20811

Cited by 148Rheumatoid Arthritis Research and TherapiesAutoimmune and Inflammatory Disorders ResearchMusculoskeletal synovial abnormalities and treatments

Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis show the imprint of synovial tissue heterogeneity: evidence of a link between an increased myofibroblast-like phenotype and high-inflammation synovitis

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Kasperkovitz, Pia V., Timmer, Trieneke C. G., Smeets, Tom J., Verbeet, Nicolette L., Tak, Paul P., van baarsen, Lisa G. M., Baltus, Belinda, Huizinga, Tom W. J. +5 more·2005·Arthritis & Rheumatism

DOI 10.1002/art.20811

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Abstract

Objective: Given the heterogeneity of gene expression patterns and cellular distribution between rheumatoid arthritis (RA) synovial tissues, we sought to determine whether this variability was also reflected at the level of the fibroblast‐like synoviocyte (FLS) cultured from RA synovial tissues. Methods: Gene expression profiles in FLS cultured from synovial tissues obtained from 19 RA patients were analyzed using complementary DNA microarrays and hierarchical cluster analysis. To validate the subclassification, we performed prediction analysis and principal components analysis. Genes that differed significantly in their expression between FLS cultures were selected using Statistical Analysis of Microarrays software. Real‐time quantitative polymerase chain reaction was performed to validate the microarray data. Immunocytochemistry was applied to study the expression of the genes of interest in FLS and synovial tissues. Results: Hierarchical clustering identified 2 main groups of FLS characterized by distinctive gene expression profiles. FLS from high‐inflammation synovial tissues revealed increased expression of a transforming growth factor β/activin A–inducible gene profile that is characteristic of myofibroblasts, a cell type considered to be involved in wound healing, whereas increased production of growth factor (insulin‐like growth factor 2/insulin‐like growth factor binding protein 5) appeared to constitute a characteristic feature of FLS derived from low‐inflammation synovial tissues. The molecular feature that defines the myofibroblast‐like phenotype was reflected as an increased proportion of myofibroblast‐like cells in the heterogeneous FLS population. Myofibroblast‐like cells were also found upon immunohistochemical analysis of synovial tissue. Conclusion: Our findings support the notion that heterogeneity between synovial tissues is reflected in FLS as a stable trait, and provide evidence of a possible link between the behavior of FLS and the inflammation status of RA synovium.

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Myofibroblasts or myofibroblast-like contractile cells have been found in several inflamed tissues, including ligament, meniscus, and tendon synovia.
“Presence of myofibroblasts, or myofibroblast-like contractile cells, has been demonstrated in several tissues during inflammation including synovia of ligaments, menisci, and tendons [27].”
From Dermal fibroblast-to-myofibroblast transition sustained by αvß3 integrin-ILK-Snail1/Slug signaling is a common feature for hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders (2018) · cites this paper as [27]

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Authors: Kasperkovitz, P. V., Timmer, T. C. G., Smeets, T. J., Verbeet, N. L., Tak, P. P., van baarsen, L. G. M., Baltus, B., Huizinga, T. W. J., Pieterman, E., Fero, M., Firestein, G. S., van der Pouw Kraan, T. C. T. M., & Verweij, C. L.
Affiliations: Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
ORCID: Kasperkovitz, Pia V.
Smeets, Tom J.
Tak, Paul P.
Huizinga, Tom W. J.
Pieterman, Elsbet
Firestein, Gary S.
Venue: Arthritis & Rheumatism
Publisher: Wiley
Published: 2005-02
Volume: 52
Issue: 2
Pages: 430-441
ISSN: 0004-3591 (ISSN-L)
1529-0131
DOI: 10.1002/art.20811
OpenAlex: W2153064758
Cited by: 148
References: 53
Citations by year: 2026: 1 · 2025: 1 · 2024: 7 · 2023: 3 · 2022: 11 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 9 · 2017: 4 · 2016: 10 · 2015: 5 · 2014: 9 · 2013: 6 · 2012: 8
FWCI: 6.30
Type: journal article
Language: en
Open access: green
research.vumc.nl
Licence: other-oa
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2 d)
Locations: Arthritis & Rheumatism (publishedVersion)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders: Universiteit Leiden
Topics: Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Health Sciences › Medicine › Rheumatology › Musculoskeletal synovial abnormalities and treatments
Keywords: rheumatoid arthritis, synovial fibroblasts, gene expression profiles, insulin-like growth factor II, IGFBP-5, synovitis
MeSH terms: Arthritis, Rheumatoid, Cells, Cultured, Fibroblasts, Humans, Immunohistochemistry, Inflammation, Phenotype, Synovial Membrane, Gene Expression, Oligonucleotide Array Sequence Analysis

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Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis show the imprint of synovial tissue heterogeneity: evidence of a link between an increased myofibroblast-like phenotype and high-inflammation synovitis

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