ArticleArthritis research & therapy2012
Transglutaminase 2 cross-linking activity is linked to invadopodia formation and cartilage breakdown in arthritis.
Article in Arthritis research & therapy, 2012. 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, 35 citations in OpenAlex.
- Molecular basis of post-translational neoantigen generation in rheumatoid arthritis: breaking immunological tolerance and implications for targeted therapy.Frontiers in immunology · 2026Review
- α9β1 integrin & its ligands as new potential biomarkers in FMF.The Indian journal of medical research · 2024Article
- The P2X7 Receptor in Autoimmunity.International journal of molecular sciences · 2023Review
- Peripheral blood cellular dynamics of rheumatoid arthritis treatment informs about efficacy of response to disease modifying drugs.Scientific reports · 2023Article
- Article
- Cytosolic TGM2 promotes malignant progression in gastric cancer by suppressing the TRIM21-mediated ubiquitination/degradation of STAT1 in a GTP binding-dependent modality.Cancer communications (London, England) · 2023Article
- 14-3-3η Promotes Invadosome Formation via the FOXO3-Snail Axis in Rheumatoid Arthritis Fibroblast-like Synoviocytes.International journal of molecular sciences · 2021Article
- Targeting MyD88 Downregulates Inflammatory Mediators and Pathogenic Processes in PBMC From DMARDs-Naïve Rheumatoid Arthritis Patients.Frontiers in pharmacology · 2021Article
- TGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma.International journal of molecular medicine · 2018Article
- ECM Cross-Linking Regulates Invadopodia Dynamics.Biophysical journal · 2018Article
- The role of α9β1 integrin and its ligands in the development of autoimmune diseases.Journal of cell communication and signaling · 2018Article
- Transglutaminase 2 in human diseases.BioMedicine · 2017Article
- Review
- Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory osteoarthritis.Amino acids · 2017Review
- Role of tissue transglutaminase in the pathogenesis of diabetic cardiomyopathy and the intervention effect of rutin.Experimental and therapeutic medicine · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
introductionThe microenvironment surrounding inflamed synovium leads to the activation of fibroblast-like synoviocytes (FLSs), which are important contributors to cartilage destruction in rheumatoid arthritic (RA) joints. Transglutaminase 2 (TG2), an enzyme involved in extracellular matrix (ECM) cross-linking and remodeling, is activated by inflammatory signals. This study was undertaken to assess the potential contribution of TG2 to FLS-induced cartilage degradation.
methodsTransglutaminase (TGase) activity and collagen degradation were assessed with the immunohistochemistry of control, collagen-induced arthritic (CIA) or TG2 knockdown (shRNA)-treated joint tissues. TGase activity in control (C-FLS) and arthritic (A-FLS) rat FLSs was measured by in situ 5-(biotinamido)-pentylamine incorporation. Invadopodia formation and functions were measured in rat FLSs and cells from normal (control; C-FLS) and RA patients (RA-FLS) by in situ ECM degradation. Immunoblotting, enzyme-linked immunosorbent assay (ELISA), and p3TP-Lux reporter assays were used to assess transforming growth factor-β (TGF-β) production and activation.
resultsTG2 and TGase activity were associated with cartilage degradation in CIA joints. In contrast, TGase activity and cartilage degradation were reduced in joints by TG2 knockdown. A-FLSs displayed higher TGase activity and TG2 expression in ECM than did C-FLSs. TG2 knockdown or TGase inhibition resulted in reduced invadopodia formation in rat and human arthritic FLSs. In contrast, increased invadopodia formation was noted in response to TGase activity induced by TGF-β, dithiothreitol (DTT), or TG2 overexpression. TG2-induced increases in invadopodia formation were blocked by TGF-β neutralization or inhibition of TGF-βR1.
conclusionsTG2, through its TGase activity, is required for ECM degradation in arthritic FLS and CIA joints. Our findings provide a potential target to prevent cartilage degradation in RA.
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