Molecular mechanisms and treatment strategies for Dupuytren&amp;rsquo;s disease

O’Gorman, David B.; Vi, Linda; Gan, Bing Siang

doi:10.2147/tcrm.s9165

Cited by 4 publications

(3 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One factor that was considerably upregulated in our study is TGF-β1 (2.53). TGF-β1 is a known stimulator in the molecular pathogenesis of fibrosis in another notable musculoskeletal fibroproliferative hand pathology, Dupuytren's contracture [42,[45][46][47]. In Dupuytren's contracture, TGF-β1 acts as a growth factor that induces fibroblast contraction within pathological tissues, leading to deformation at the cellular level [48].…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β1-mediated Wnt signaling has been proven in other studies to regulate fibroproliferation in lung fibrosis, renal fibrosis, skin fibrosis, musculoskeletal fibrosis, and liver fibrosis which could potentially mediate fibrosis in trigger finger [51,52]. Lederhose disease [53,54], adhesive capsulitis [55][56][57], and Peyronie's disease [45,58,59] are prominent fibroproliferative disorders that share molecular characteristics with Dupuytren's contracture. We believe that the trigger finger also shares many of the same molecular characteristics as these fibrotic disorders.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nanostring-Based Identification of the Gene Expression Profile in Trigger Finger Samples

et al. 2021

View full text Add to dashboard Cite

Trigger finger is a common yet vastly understudied fibroproliferative hand pathology, severely affecting patients’ quality of life. Consistent trauma due to inadequate positioning within the afflicted finger’s tendon/pulley system leads to cellular dysregulation and eventual fibrosis. While the genetic characteristics of the fibrotic tissue in the trigger finger have been studied, the pathways that govern the initiation and propagation of fibrosis are still unknown. The complete gene expression profile of the trigger finger has never been explored. Our study has used the Nanostring nCounter gene expression assay to investigate the molecular signaling involved in trigger finger pathogenesis. We collected samples from patients undergoing trigger finger (n = 4) release surgery and compared the gene expression to carpal tunnel tissue (n = 4). Nanostring nCounter analysis identified 165 genes that were differentially regulated; 145 of these genes were upregulated, whereas 20 genes were downregulated. We found that several collagen genes were significantly upregulated, and a regulatory matrix metalloproteinase (MMP), MMP-3, was downregulated. Bioinformatic analysis revealed that several known signaling pathways were dysregulated, such as the TGF-β1 and Wnt signaling pathways. We also found several novel signaling pathways (e.g., PI3K, MAPK, JAK-STAT, and Notch) differentially regulated in trigger finger. The outcome of our study helps in understanding the molecular signaling pathway involved in the pathogenesis of the trigger finger.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nanostring-Based Identification of the Gene Expression Profile in Trigger Finger Samples

et al. 2021

View full text Add to dashboard Cite

show abstract

“… 2 Latest research suggests a greater focus on genetics 3 , 4 and molecular biology. 2 , 5 , 6 Hindocha et al 7 described 5 statistical risk factors for recurrence of the disease after treatment: family history, bilateral occurrence, ectopic lesions, male sex, and age of onset ≤50 years. According to the literature, surgery is the most widely accepted option to treat contractures in DD.…”

Section: Introductionmentioning

confidence: 99%

Multiple Recurrences in Aggressive Forms of Dupuytren’s Disease—Can Patients Benefit from Repeated Selective Fasciectomy?

Könneker

Broelsch

Krezdorn

et al. 2017

Plastic and Reconstructive Surgery - Global Open

View full text Add to dashboard Cite

Background:In Dupuytren’s disease (DD), limited fasciectomy is the mainstay of surgical therapy in patients at risk of contractures and disease recurrences. New minimally invasive treatments such as injection of collagenase clostridium histolyticum have evolved as a common tool for the preliminary treatment of Dupuytren’s contractures. However, recurrences and their therapy remain controversial. In this study, we evaluate the benefit of repeated limited fasciectomy in patients with aggressive forms of the disease and multiple recurrences of contractures.Methods:We evaluated the outcome of 16 patients undergoing limited fasciectomy 3 or more times on a single hand.Results:Postoperatively, 10 of 13 (76.9%) patients were satisfied with the clinical result after the last operation; 10 of 12 (83.3%) patients would choose to have their surgery repeated, if so needed. The mean improvement of proximal interphalangeal joint range of motion was 59.2 degrees (SD 26.8) and 86.2% (SD 19.9). There were no severe complications after treatment within the observed time period.Conclusions:Our findings demonstrate that patients with recurrence of contractures after multiple previous treatments in aggressive forms of DD can benefit from surgical intervention. In conclusion, repeated limited fasciectomy remains indicated in patients after previous surgeries with DD.

show abstract

The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix

et al. 2019

View full text Add to dashboard Cite

Fibrotic diseases, such as Dupuytren’s contracture (DC), involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts is a significant mechanism in DC, as it generates tissue contraction in areas without wound openings, leading to the deposition of scar tissue, and eventually flexing one or more fingers in a restrictive fashion. Additionally, DC has a high recurrence rate. Previously, we showed that N-dihydrogalactochitosan (GC), an immunostimulant, inhibited myofibroblast differentiation in a DC fibroblast culture. Our goal of this study was to expand our previous study to include other DC and normal cell lines and other chitosan derivatives (GC and single-walled carbon nanotube-conjugated GC) to determine the specific mechanism of inhibition. Derivative-incorporated and vehicle control (water) anchored fibroblast-populated collagen matrices (aFPCM) were used to monitor compaction (anchored matrix height reduction) using microscopy and optical coherence tomography (OCT) for six days. Fibroblasts were unable to compact chitosan derivative aFPCM to the same extent as vehicle control aFPCM in repeated experiments. Similarly, chitosan derivative aFPCM contracted less than control aFPCM when released from anchorage. Proliferative myofibroblasts were identified by the presence of alpha smooth muscle actin via myofibroblast proliferative assay. In all tested conditions, a small percentage of myofibroblasts and proliferative cells were present. However, when aFPCM were treated with transforming growth factor-beta 1 (TGF-β1), all tested samples demonstrated increased myofibroblasts, proliferation, compaction, and contraction. Although compaction and contraction were reduced, there was sufficient tension present in the chitosan derivative aFPCM to allow exogenous stimulation of the myofibroblast phenotype.

show abstract

Molecular mechanisms and treatment strategies for Dupuytren’s disease

Cited by 4 publications

References 90 publications

Nanostring-Based Identification of the Gene Expression Profile in Trigger Finger Samples

Nanostring-Based Identification of the Gene Expression Profile in Trigger Finger Samples

Multiple Recurrences in Aggressive Forms of Dupuytren’s Disease—Can Patients Benefit from Repeated Selective Fasciectomy?

The Effect of Chitosan Derivatives on the Compaction and Tension Generation of the Fibroblast-populated Collagen Matrix

Contact Info

Product

Resources

About