ArticleArthritis research & therapy2015
Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism.
Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- A Compartmentalized Joint-on-chip (JoC) Model to Unravel the Contribution of Cartilage and Synovium to Osteoarthritis Pathogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulation of fibroblast-like synoviocyte function by cadherin 6 in rheumatoid arthritis.Arthritis research & therapy · 2025Article
- A framework of biomarkers for skeletal aging: a consensus statement by the Aging Biomarker Consortium.Life medicine · 2023Article
- Cadherin-11 increases tumor cell proliferation and metastatic potential via Wnt pathway activation.Molecular oncology · 2023Article
- Stem Cells in Autologous Microfragmented Adipose Tissue: Current Perspectives in Osteoarthritis Disease.International journal of molecular sciences · 2021Review
- Research progress in the role and mechanism of Cadherin-11 in different diseases.Journal of Cancer · 2021Review
- Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes.Nature reviews. Rheumatology · 2020Review
- Interactions between cadherin-11 and platelet-derived growth factor receptor-alpha signaling link cell adhesion and proliferation.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis.International journal of molecular sciences · 2019Review
- Cadherin 11 Inhibition Downregulates β-catenin, Deactivates the Canonical WNT Signalling Pathway and Suppresses the Cancer Stem Cell-Like Phenotype of Triple Negative Breast Cancer.Journal of clinical medicine · 2019Article
- Cadherin-11 as a regulator of valve myofibroblast mechanobiology.American journal of physiology. Heart and circulatory physiology · 2018Article
- The Tumor-Like Phenotype of Rheumatoid Synovium: Molecular Profiling and Prospects for Precision Medicine.Arthritis & rheumatology (Hoboken, N.J.) · 2018Review
- Synovial cellular and molecular markers in rheumatoid arthritis.Seminars in immunopathology · 2017Review
- Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration.The American journal of pathology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionEngagement of the homotypic cell-to-cell adhesion molecule cadherin-11 on rheumatoid arthritis (RA) synovial fibroblasts with a chimeric molecule containing the cadherin-11 extracellular binding domain stimulated cytokine, chemokine, and matrix metalloproteinases (MMP) release, implicating cadherin-11 signaling in RA pathogenesis. The objective of this study was to determine if cadherin-11 extracellular domain fragments are found inside the joint and if a physiologic synovial fibroblast cleavage pathway releases those fragments.
methodsCadherin-11 cleavage fragments were detected by western blot in cell media or lysates. Cleavage was interrupted using chemical inhibitors or short-interfering RNA (siRNA) gene silencing. The amount of cadherin-11 fragments in synovial fluid was measured by western blot and ELISA.
resultsSoluble cadherin-11 extracellular fragments were detected in human synovial fluid at significantly higher levels in RA samples compared to osteoarthritis (OA) samples. A cadherin-11 N-terminal extracellular binding domain fragment was shed from synovial fibroblasts after ionomycin stimulation, followed by presenilin 1 (PSN1)-dependent regulated intramembrane proteolysis of the retained membrane-bound C-terminal fragments. In addition to ionomycin-induced calcium flux, tumor necrosis factor (TNF)-α also stimulated cleavage in both two- and three-dimensional fibroblast cultures. Although cadherin-11 extracellular domains were shed by a disintegrin and metalloproteinase (ADAM) 10 in several cell types, a novel ADAM- and metalloproteinase-independent activity mediated shedding in primary human fibroblasts.
conclusionsCadherin-11 undergoes ectodomain shedding followed by regulated intramembrane proteolysis in synovial fibroblasts, triggered by a novel sheddase that generates extracelluar cadherin-11 fragments. Cadherin-11 fragments were enriched in RA synovial fluid, suggesting they may be a marker of synovial burden and may function to modify cadherin-11 interactions between synovial fibroblasts.
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