ArticleJournal of immunology (Baltimore, Md. : 1950)2017
Constitutive Activation of Integrin α9 Augments Self-Directed Hyperplastic and Proinflammatory Properties of Fibroblast-like Synoviocytes of Rheumatoid Arthritis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- ASP5094, a humanized monoclonal antibody against integrin alpha-9, did not show efficacy in patients with rheumatoid arthritis refractory to methotrexate: results from a phase 2a, randomized, double-blind, placebo-controlled trial.Arthritis research & therapy · 2020Trial
- Integrin αVβ3 as a context‑dependent regulator of bone homeostasis: Insights into osteoporosis pathogenesis and therapeutic targeting (Review).Molecular medicine reports · 2026Review
- Modeling Tenascin-C-rich metastatic tumor niches in engineered hydrogel biomaterials.Acta biomaterialia · 2026Article
- Increased TNN in Knee Osteoarthritis Accelerates Cartilage Damage via the Negative Regulation of AMPK-PPARγ Signalling.Journal of cellular and molecular medicine · 2025Article
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
- Decreased plasma gelsolin fosters a fibrotic tumor microenvironment and promotes chemoradiotherapy resistance in esophageal squamous cell carcinoma.Journal of biomedical science · 2024Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Targeting fibroblast-like synoviocytes in rheumatoid arthritis.Current opinion in pharmacology · 2022Review
- Review
- Integrin α9 regulates smooth muscle cell phenotype switching and vascular remodeling.JCI insight · 2021Article
- Destructive Roles of Fibroblast-like Synoviocytes in Chronic Inflammation and Joint Damage in Rheumatoid Arthritis.Inflammation · 2021Review
- Cytohesin-2/ARNO: A Novel Bridge Between Cell Migration and Immunoregulation in Synovial Fibroblasts.Frontiers in immunology · 2021Article
- Integrin-α9β1 as a Novel Therapeutic Target for Refractory Diseases: Recent Progress and Insights.Frontiers in immunology · 2021Review
- Integrin-α9 and Its Corresponding Ligands Play Regulatory Roles in Chronic Periodontitis.Inflammation · 2020Article
- Shedding New Light on The Role of ανβ3 and α5β1 Integrins in Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2019Review
- βInflammopharmacology · 2019Article
- Regulation of Immune Responses and Chronic Inflammation by Fibroblast-Like Synoviocytes.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite advances in the treatment of rheumatoid arthritis (RA), currently approved medications can have significant side effects due to their direct immunosuppressive activities. Additionally, current therapies do not address residual synovial inflammation. In this study, we evaluated the role of integrin α9 and its ligand, tenascin-C (Tn-C), on the proliferative and inflammatory response of fibroblast-like synoviocytes (FLSs) from RA patients grown in three-dimensional (3D)-micromass culture. FLSs from osteoarthritis patients, when grown in the 3D-culture system, formed self-directed lining-like structures, whereas FLSs from RA tissues (RA-FLSs) developed an abnormal structure of condensed cellular accumulation reflective of the pathogenic features of RA synovial tissues. Additionally, RA-FLSs grown in 3D culture showed autonomous production of proinflammatory mediators. Predominant expression of α9 and Tn-C was observed in the condensed lining, and knockdown of these molecules abrogated the abnormal lining-like structure formation and suppressed the spontaneous expression of matrix metalloproteinases, IL-6, TNFSF11/RANKL, and cadherin-11. Disruption of α9 also inhibited expression of Tn-C, suggesting existence of a positive feedback loop in which the engagement of α9 with Tn-C self-amplifies its own signaling and promotes progression of synovial hyperplasia. Depletion of α9 also suppressed the platelet-derived growth factor-induced hyperplastic response of RA-FLSs and blunted the TNF-α-induced expression of matrix metalloproteinases and IL-6. Finally, α9-blocking Ab also suppressed the formation of the condensed cellular lining by RA-FLSs in 3D cultures in a concentration-related manner. This study demonstrates the central role of α9 in pathogenic behaviors of RA-FLSs and highlights the potential of α9-blocking agents as a nonimmunosuppressive treatment for RA-associated synovitis.
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