ArticleProceedings of the National Academy of Sciences of the United States of America2013
Unraveling the signaling pathways promoting fibrosis in Dupuytren's disease reveals TNF as a therapeutic target.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 3 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Fibroproliferative disorders and diabetes: Understanding the pathophysiologic relationship between Peyronie's disease, Dupuytren disease and diabetes.Endocrinology, diabetes & metabolism · 2021Pooled it
- What do we know about managing Dupuytren's disease cost-effectively?BMC musculoskeletal disorders · 2018Pooled it
- Systematic review of non-surgical treatments for early dupuytren's disease.BMC musculoskeletal disorders · 2016Pooled it
- Progression of Dupuytren Contracture: A Randomized Controlled Trial Comparing Surgery, Needle Fasciotomy, and Collagenase Injection.Plastic and reconstructive surgery · 2026Trial
- Anti-Tumour Necrosis Factor Therapy for Dupuytren's Disease: A Randomised Dose Response Proof of Concept Phase 2a Clinical Trial.EBioMedicine · 2018Trial
- S100A4-TLR4-TGF-β axis as a therapeutic target for Dupuytren's contracture in diabetic patients.Cell death discovery · 2026Article
- Uncoupling TGFβ1 signalling from collagen protein synthesis in Dupuytren's disease.The Journal of pathology · 2026Article
- Development of a 3D In Vitro Model of Dupuytren's Disease as a Platform for Drug Screening.Cellular and molecular bioengineering · 2026Article
- Transforming Myofibroblasts Into Lipid-Filled Cells to Treat Dupuytren Disease.The Journal of hand surgery · 2026Article
- Article
- Palmar Fascia Fibrosis in Dupuytren's Disease: A Narrative Review of Pathogenic Mechanisms and Molecular Insights.International journal of molecular sciences · 2025Review
- TNF-α represses fibroblast to myofibroblast transition through the histone methyltransferase Setdb2.JCI insight · 2025Article
- Plantar Fibromatosis/Fascitis in Ankylosing Spondylitis: Why/Where to Inject?European journal of rheumatology · 2025Article
- Active synthesis of type I collagen homotrimer in Dupuytren's fibrosis is unaffected by anti-TNF-α treatment.JCI insight · 2025Article
- Pathological Changes in Extracellular Matrix Composition Orchestrate the Fibrotic Feedback Loop Through Macrophage Activation in Dupuytren's Contracture.International journal of molecular sciences · 2025Article
- Periarticular myositis and muscle fibrosis are cytokine-dependent complications of inflammatory arthritis.JCI insight · 2025Article
- The endocannabinoid system as a therapeutic target in intestinal fibrosis.Frontiers in pharmacology · 2025Review
- Alterations in the Structure, Composition, and Organization of Galactosaminoglycan-Containing Proteoglycans and Collagen Correspond to the Progressive Stages of Dupuytren's Disease.International journal of molecular sciences · 2024Article
- C-X-C domain ligand 14-mediated stromal cell-macrophage interaction as a therapeutic target for hand dermal fibrosis.Communications biology · 2023Article
- Let's Focus on the Fibrosis in Dupuytren Disease: Cell Communication Network Factor 2 as a Novel Target.Journal of hand surgery global online · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dupuytren's disease is a very common progressive fibrosis of the palm leading to flexion deformities of the digits that impair hand function. The cell responsible for development of the disease is the myofibroblast. There is currently no treatment for early disease or for preventing recurrence following surgical excision of affected tissue in advanced disease. Therefore, we sought to unravel the signaling pathways leading to the development of myofibroblasts in Dupuytren's disease. We characterized the cells present in Dupuytren's tissue and found significant numbers of immune cells, including classically activated macrophages. High levels of proinflammatory cytokines were also detected in tissue from Dupuytren's patients. We compared the effects of these cytokines on contraction and profibrotic signaling pathways in fibroblasts from the palmar and nonpalmar dermis of Dupuytren's patients and palmar fibroblasts from non-Dupuytren's patients. Exogenous addition of TNF, but not other cytokines, including IL-6 and IL-1β, promoted differentiation into specifically of palmar dermal fibroblasts from Dupuytren's patients in to myofibroblasts. We also demonstrated that TNF acts via the Wnt signaling pathway to drive contraction and profibrotic signaling in these cells. Finally, we examined the effects of targeted cytokine inhibition. Neutralizing antibodies to TNF inhibited the contractile activity of myofibroblasts derived from Dupuytren's patients, reduced their expression of α-smooth muscle actin, and mediated disassembly of the contractile apparatus. Therefore, we showed that localized inflammation in Dupuytren's disease contributes to the development and progression of this fibroproliferative disorder and identified TNF as a therapeutic target to down-regulate myofibroblast differentiation and activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.