ArticleArthritis and rheumatism2008
The arthritis severity locus Cia5d is a novel genetic regulator of the invasive properties of synovial fibroblasts.
Article in Arthritis and rheumatism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- DLX4 regulates rheumatoid arthritis fibroblast-like synoviocytes invasiveness and a cancer transcriptomic signature.Scientific reports · 2025Article
- Article
- BACH1 as a key driver in rheumatoid arthritis fibroblast-like synoviocytes identified through gene network analysis.Life science alliance · 2025Article
- Gene Network Analyses Identify Co-regulated Transcription Factors and BACH1 as a Key Driver in Rheumatoid Arthritis Fibroblast-like Synoviocytes.bioRxiv : the preprint server for biology · 2024Article
- KIF1C and new Huntingtin-interacting protein 1 binding proteins regulate rheumatoid arthritis fibroblast-like synoviocytes' phenotypes.Frontiers in immunology · 2024Article
- Combination therapy of a TRPV2 agonist with a TNF inhibitor achieves sustained suppression of disease severity and reduced joint damage.Clinical and experimental immunology · 2023Article
- A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment.Cellular and molecular life sciences : CMLS · 2023Review
- Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats.Frontiers in pharmacology · 2021Article
- Antioxidant Carbon Nanoparticles Inhibit Fibroblast-Like Synoviocyte Invasiveness and Reduce Disease Severity in a Rat Model of Rheumatoid Arthritis.Antioxidants (Basel, Switzerland) · 2020Article
- Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes.Nature reviews. Rheumatology · 2020Review
- KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis.Arthritis research & therapy · 2019Article
- Jatrorrhizine Hydrochloride Suppresses Proliferation, Migration, and Secretion of Synoviocytes In Vitro and Ameliorates Rat Models of Rheumatoid Arthritis In Vivo.International journal of molecular sciences · 2018Article
- Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.Nature communications · 2018Article
- Targeting KCa1.1 Channels with a Scorpion Venom Peptide for the Therapy of Rat Models of Rheumatoid Arthritis.The Journal of pharmacology and experimental therapeutics · 2018Article
- Suppression and resolution of autoimmune arthritis by rhesus θ-defensin-1, an immunomodulatory macrocyclic peptide.PloS one · 2017Article
- Different expression of β subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes.Arthritis research & therapy · 2016Article
- Receptor Protein Tyrosine Phosphatase α-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of Arthritis in Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- TGFβ responsive tyrosine phosphatase promotes rheumatoid synovial fibroblast invasiveness.Annals of the rheumatic diseases · 2016Article
- The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion.Clinical immunology (Orlando, Fla.) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe synovial fibroblast, or fibroblast-like synoviocyte (FLS), has a central role in pannus invasion and destruction of cartilage and bone in rheumatoid arthritis (RA). However, regulation of the FLS remains incompletely understood. The aim of this study was to determine whether the invasive properties of FLS are genetically regulated by arthritis severity loci.
methodsDA rats (arthritis susceptible) and rat strains congenic for arthritis-protective intervals were studied. Primary FLS cell lines were generated from each strain and used in a well-established FLS invasion model through a collagen-rich barrier. Cells or culture supernatants were analyzed for gene expression, activity of different matrix metalloproteinases (MMPs), cytoskeleton integrity, and cell proliferation.
resultsThe median number of FLS from DA.F344(Cia5d) rats that invaded through the collagen-rich barrier was reduced 86.5% compared with the median number of invading FLS from DA rats. Histologic examination showed that DA.F344(Cia5d) rats preserved a normal joint without pannus, hyperplasia, or erosions. FLS from DA.F344(Cia5d) rats produced significantly lower levels of active MMP-2 compared with FLS from DA rats, but the levels of proMMP-2 and MMP-2 messenger RNA in DA.F344(Cia5d) rats were similar to those in DA rats. Treatment of FLS from DA rats with an MMP-2 inhibitor reduced cell invasion to a level similar to that in DA.F344(Cia5d) rats, demonstrating that MMP-2 activity accounted for the difference between FLS from these 2 strains. Analysis of MMP-2-activating pathways revealed increased levels of soluble membrane type 1 (MT1)-MMP in DA rats compared with DA.F344(Cia5d) rats.
conclusionThese data represent the first evidence for a genetic component in the regulation of FLS invasion. A gene located within the Cia5d interval accounts for this effect and operates via the regulation of soluble MT1-MMP production and MMP-2 activation. These observations suggest novel potential pathways for prognostication and therapy.
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