Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes

@article{Nygaard2020RestoringSH,
  title={Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes},
  author={Gyrid Nygaard and Gary S. Firestein},
  journal={Nature Reviews Rheumatology},
  year={2020},
  volume={16},
  pages={316-333}
}
Rheumatoid arthritis (RA) is a chronic immune-mediated disease that primarily affects the synovium of diarthrodial joints. During the course of RA, the synovium transforms into a hyperplastic invasive tissue that causes destruction of cartilage and bone. Fibroblast-like synoviocytes (FLS), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype in RA and have an important role in these pathological processes. In addition to producing the extracellular… 
Destructive Roles of Fibroblast-like Synoviocytes in Chronic Inflammation and Joint Damage in Rheumatoid Arthritis.
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The study revealed data about interactions between RA FLS and immune/non-immune cells as well as the role ofRA FLS cells in joint damage, ELS formation, and neoangiogenesis, which provide useful information for developing new approaches for RA treatment.
Fibroblast Like Synovial Cell Subsets in Rheumatoid Arthritis
TLDR
Evidence of FLS as active players in RA pathology capable of cellular recruitment, local cellular crosstalk and promotion of joint destruction is supported, supported by studies isolating and characterizing gene expression in synovial FLS.
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TLDR
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Targeting FLS signalling in RA
  • J. McHugh
  • Medicine
    Nature Reviews Rheumatology
  • 2020
TLDR
The expression of DDr2 correlated with the expression of iL-15 and DKK1 both in FLs from patients with ra (ra FLs) and in mice with collagen antibodyinduced arthritis (Caia), which highlighted the involvement of a signalling axis downstream of discoidin domain receptor 2 (DDr2) in this process.
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TLDR
This review discusses the recent advances in the understanding of how fibroblast heterogeneity contributes to joint pathology in rheumatoid arthritis and addresses how these insights could lead to the development of novel therapies that directly target selective populations of fibroblasts in the future.
Caspase-8 Variant G Regulates Rheumatoid Arthritis Fibroblast-Like Synoviocyte Aggressive Behavior.
TLDR
Epigenetic and transcriptomic analyses of RA FLSs revealed that a specific caspase-8 isoform, variant G, is the dominant isoform expressed and induced by PDGF, and could decrease cell invasion in diseases like RA without the potential deleterious effects of nonspecific casp enzyme-8 inhibition.
ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype
TLDR
Interestingly however, DNA methylome analysis reveals that rather than simply preventing the pathogenic rewiring of SFs, ES-62 induces further epigenetic remodelling, including targeting genes associated with ciliogenesis and differentiation, to program a distinct “protective” phenotype.
SFRP5 Enhances Wnt5a Induced-Inflammation in Rheumatoid Arthritis Fibroblast-Like Synoviocytes
TLDR
It is demonstrated that Wnt5a stimulated the expression of the pro-inflammatory targets, especially IL1β, IL8 and IL6 in RA td-FLS and inhibited the gene expression of TCF4 and the protein levels of the canonical coreceptor LRP5.
Role of glucose metabolism in aggressive phenotype of fibroblast-like synoviocytes: Latest evidence and therapeutic approaches in rheumatoid arthritis.
TLDR
The current knowledge about glucose metabolism of FLS cells is summarized and novel biomarkers, which are potential candidates for RA treatment, are suggested.
Expression of extracellular matrix components and cytokine receptors in human fibrocytes during rheumatoid arthritis
TLDR
Evaluated the morphology of fibrocytes in vitro and their ability to produce different extracellular matrix (ECM) components in comparison with two populations of rheumatoid arthritis FLS found that fibronectin and MMP3 levels were higher in FLS compared to fibroCytes.
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References

SHOWING 1-10 OF 254 REFERENCES
The role and therapeutic implications of fibroblast‐like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis
TLDR
The ability of FLS to stimulate both inflammation and tissue damage suggests that this cell type may be a unique target for the treatment of inflammatory arthritis.
Fibroblast‐like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin‐11
TLDR
It is suggested that FLS are critical regulators of synovial inflammation and arthritis pathology via mechanisms that are mediated by cadherin‐11.
Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors
TLDR
The dual behaviour of FLS in RA suggests that FLS- directed therapies could become a complementary approach to immune-directed therapies in this disease, and progress in targeting these cells is reviewed.
Targeting phosphatase-dependent proteoglycan switch for rheumatoid arthritis therapy
TLDR
It is demonstrated that FLS are regulated by an RPTPσ-dependent proteoglycan switch in vivo, which can be targeted for RA therapy and envisioned that therapies targeting the proteogly can switch or its intracellular pathway in FLS could be effective as a monotherapy or in combination with currently available immune-targeted agents to improve control of disease activity in RA patients.
Fibroblast‐like synoviocytes: key effector cells in rheumatoid arthritis
TLDR
Rheumatoid FLS develop a unique aggressive phenotype that increases invasiveness into the extracellular matrix and further exacerbates joint damage, and new agents that target FLS could potentially complement the current therapies without major deleterious effect on adaptive immune responses.
The arthritis severity locus Cia5d is a novel genetic regulator of the invasive properties of synovial fibroblasts.
TLDR
These data represent the first evidence for a genetic component in the regulation of FLS invasion and suggest novel potential pathways for prognostication and therapy.
Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis
TLDR
It is shown that fibroblast-like synoviocytes in rheumatoid arthritis differ from healthy synovial fibroblasts, not only in their marker expression, proto-oncogene expression, or their epigenetic changes, but also in their intracellular metabolism.
PUMA gene delivery to synoviocytes reduces inflammation and degeneration of arthritic joints
TLDR
Targeting of synoviocytes by a vector, consisting of a baculovirus conjugated to an adenovirus carrying the pro-apoptotic gene PUMA, has therapeutic efficacy in a rat arthritis model and demonstrates the therapeutic potential of PUMA gene therapy as a local treatment in various forms of arthritis.
Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis.
TLDR
The ex vivo invasive behavior of FLS from RA patients is associated with the rate of joint destruction and is a patient characteristic, given the much smaller intraindividual than interindividual FLS variation.
Epigenetic alterations in rheumatoid arthritis fibroblast-like synoviocytes.
TLDR
The epigenetic changes (DNA methylation, histone modification and miRNA expression) in fibroblast-like synoviocytes, which are the joint-lining mesenchymal cells that play an important role in joint inflammation and damage are summarized.
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2
3
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5
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