Dupuytren Disease

Rayan, Ghazi M.

doi:10.2106/00004623-200701000-00026

Cited by 139 publications

(30 citation statements)

References 80 publications

(82 reference statements)

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“…Most surgeries were performed by a hand specialist or hand surgeon, and fasciectomy was the most frequent type of surgery performed. In the literature, surgery is the most common treatment for Dupuytren’s [15–17, 21], and fasciectomy is the most common procedure [15]. Prolonged postoperative rehabilitation, including hand therapy and splinting to improve the range of motion of the hand, is necessary to maintain the benefits of surgery [7, 15].…”

Section: Discussionmentioning

confidence: 99%

Prevalence, Incidence, and Treatments of Dupuytren's Disease in the United States: Results from a Population-Based Study

DiBenedetti

Nguyen²,

Zografos

et al. 2010

Hand (New York, N,Y.)

112

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BackgroundThis large population-based study was conducted to estimate the prevalence of Dupuytren’s disease in US adults and describe associated treatment patterns.MethodsA total of 23,103 individuals from an Internet-based research panel representative of the US population completed a brief online survey designed to identify individuals with symptoms, diagnoses, and/or treatment experience indicative of Dupuytren’s disease (mean age = 50 years).ResultsThe prevalence of Dupuytren’s disease defined as a self-reported physician diagnosis and/or surgical treatment was estimated as 1% (95% CI = 0.8–1.2), but the estimated prevalence is much higher (7.3%) when including self-reported symptoms of ropelike growth or hard bumps on the hand. The annual incidence proportion was estimated at about 3 cases per 10,000 adults. A total of 326 participants who reported relevant Dupuytren’s symptoms, treatment, and/or diagnosis completed a more in-depth survey focusing on timing of medical treatments after first symptom noticed, description of functional impairment, treatment patterns, and family history. From the second survey, most patients who reported seeking treatment for hand symptoms initially saw a primary care physician, and the mean time from noticing the first hand symptom to seeing a doctor was 23.1 months. At their first doctor visit for hand symptoms, only 9% of patients received a diagnosis of Dupuytren’s disease and 48% were advised to “wait and see” or received no treatment.ConclusionsResults from the current study indicate a number of unmet medical needs, so strategies to raise physician awareness of disease symptoms and effective treatment options may be helpful.

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Section: Discussionmentioning

confidence: 99%

Prevalence, Incidence, and Treatments of Dupuytren's Disease in the United States: Results from a Population-Based Study

DiBenedetti

Nguyen²,

Zografos

et al. 2010

Hand (New York, N,Y.)

112

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“…Dupuytren’s disease (DD) is a common fibroproliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers [1]. DD is considered to be caused by a defect in the process of wound healing or by an excessive or abnormal response to wounding [2].…”

Section: Introductionmentioning

confidence: 99%

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

Zhou

Liu

Gallo

et al. 2016

BMC Musculoskelet Disord

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BackgroundDupuytren’s disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren’s fibrosis.MethodsFibroblasts harvested from (DD) and carpal tunnel (CT)- tissues were treated with or without TGF-β1 and/or PFD and were subjected to cell migration, cell proliferation and cell contraction assays. ELISA; western blots and real time RT-PCR assays were performed to determine the levels of fibronectin; p-Smad2/Smad3; alpha-smooth muscle actin (α-SMA), α2 chain of type I collagen and α1 chain of type III collagen respectively.ResultsOur results show that PFD effectively inhibits TGF-β1-induced cell migration, proliferation and cell contractile properties of both CT- and DD-derived fibroblasts. TGF-β1−induced α-SMA mRNA and protein levels were inhibited at the higher concentration of PFD (800 μg/ml). Interestingly, TGF-β1 induction of type I and type III collagens and fibronectin was inhibited by PFD in both CT- and DD- derived fibroblasts, but the effect was more prominent in DD cells. PFD down-regulated TGF-β1-induced phosphorylation of Smad2/Smad3, a key factor in the TGF-β1 signaling pathway.ConclusionTaken together these results suggest the PFD can potentially prevent TGF-β1−induced fibroblast to myofibroblast transformation and inhibit ECM production mainly Type I- and Type III- collagen and fibronectin in DD-derived fibroblasts. Further in-vivo studies with PFD may lead to a novel therapeutic application in preventing the progression or recurrence of Dupuytren’s disease.

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“…The nodule is a key diagnostic feature and represents the early proliferative stage of the disease. The nodules contain mostly myofibroblasts [1,2]. As the disease progresses, the nodules may disappear and give way to the formation of cords.…”

Section: Introductionmentioning

confidence: 99%

“…Because of high recurrence rates following surgery, investigations are underway to determine the underlying causes of DD to optimise treatment strategies [1,2]. The myofibroblast, a specialised fibroblast phenotype that expresses α-smooth muscle actin (α-SMA), provides the cell with contractile activity [3-5].…”

Section: Introductionmentioning

confidence: 99%

Elevated transforming growth factor β and mitogen-activated protein kinase pathways mediate fibrotic traits of Dupuytren's disease fibroblasts

Krause

Kloen

Dijke

2011

Fibrogenesis Tissue Repair

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BackgroundDupuytren's disease is a fibroproliferative disorder of the palmar fascia. The treatment used to date has mostly been surgery, but there is a high recurrence rate. Transforming growth factor β (TGF-β) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in Dupuytren's disease.ResultsWe studied Dupuytren's fibroblasts in tissues ex vivo and in cells cultured in vitro and found increased TGF-β expression compared to control fibroblasts. This correlated not only with elevated expression and activation of downstream Smad effectors but also with overactive extracellular signal-regulated kinase 1/2 (ERK1/2)/mitogen-activated protein (MAP) kinase signalling. Treatment with the TGF-β type I receptor kinase inhibitor SB-431542 and bone morphogenetic protein 6 (BMP6) led to inhibition of elevated Smad and ERK1/2/MAP kinase signalling as well as to inhibition of the increased contractility of Dupuytren's fibroblasts. BMP6 attenuated TGF-β expression in Dupuytren's fibroblasts, but not in control fibroblasts. Platelet-derived growth factor (PDGF) expression was strongly promoted by TGF-β in Dupuytren's fibroblasts and was curbed by SB-431542 or BMP6 treatment. High basal expression of phosphorylated ERK1/2 MAP kinase and fibroproliferative markers was attenuated in Dupuytren's fibroblasts by a selective PDGF receptor kinase inhibitor. Cotreatment of Dupuytren's fibroblasts with SB-431542 and the mitogen-activated protein kinase kinase 1 inhibitor PD98059 was sufficient to abrogate proliferation and contraction of Dupuytren's fibroblasts.ConclusionsBoth TGF-β and ERK1/2 MAP kinase pathways cooperated in mediating the enhanced proliferation and high spontaneous contraction of Dupuytren's fibroblasts. Our data indicate that both signalling pathways are prime targets for the development of nonsurgical intervention strategies to treat Dupuytren's disease.

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Dupuytren Disease

Cited by 139 publications

References 80 publications

Prevalence, Incidence, and Treatments of Dupuytren's Disease in the United States: Results from a Population-Based Study

Prevalence, Incidence, and Treatments of Dupuytren's Disease in the United States: Results from a Population-Based Study

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

Elevated transforming growth factor β and mitogen-activated protein kinase pathways mediate fibrotic traits of Dupuytren's disease fibroblasts

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