scholarly journals Active synthesis of collagen (I) homotrimer and matrisomal proteins in Dupuytren’s fibrosis

2020 ◽  
Author(s):  
Kate Williamson ◽  
Gabriella Cooper ◽  
Katie J. Lee ◽  
Emma L. Beamish ◽  
Deborah Simpson ◽  
...  

AbstractDupuytren’s disease is a common fibroproliferative disease of the palmar fascia of the hand with severe cases treated surgically. The rate of disease recurrence following treatment is high and a continual production of matrisomal proteins could lead to disease recurrence. There is no animal model for Dupuytren’s disease, but analysis of the surgically excised tissue provides an accessible means to study the mechanisms of human tissue fibrosis. Here we sought to determine how new synthesis and the composition of matrisomal proteins in Dupuytren’s differs from normal palmar fascia samples, using metabolic labelling approaches and proteomics. Model non-fibrotic, but fibrous connective tissues, equine flexor tendon and canine cranial cruciate ligament, were used to analyse active collagen-1 protein synthesis in development, ageing and degenerative disease, where it was restricted to early development and ruptured tissue. Dupuytren’s tissue was shown to actively synthesise type I collagen, a proportion of which comprised abnormal collagen (I) homotrimer (mean 14.3% ± 14.4), as well as fibronectin, matrix metalloproteinases (MMP2, MMP3) and their inhibitors; Tissue Inhibitor of Metalloproteinases 2 (TIMP2). Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) was actively synthesised by Dupuytren’s as well as control tissue. Label-free analysis implicated the TGFβ pathway in the matrisomal profile of Dupuytren’s tissue whilst myocilin, a Wnt-pathway regulator, was noticeably more abundant in control samples. No collagen (I) neopeptides representing the major collagenase cleavage site were identified, however periostin neopeptides were abundant in Dupuytren’s tissue and gelatin neopeptides in both tissue types. Synthesis of MMP-resistant collagen-1 homotrimer, together with altered TGFβ and Wnt signalling environments, could contribute to the persistence of the fibrotic tissue and disease recurrence following treatment.

2008 ◽  
Vol 36 (12) ◽  
pp. 2432-2436 ◽  
Author(s):  
Shwan Khoschnau ◽  
Håkan Melhus ◽  
Annica Jacobson ◽  
Hans Rahme ◽  
Henrik Bengtsson ◽  
...  

Background Cruciate ligament ruptures and shoulder dislocations are often caused by trauma, but predisposing intrinsic factors might also influence the risk. These injuries are more common in those with a previously injured sibling, an observation that might indicate a genetic predisposition. It is well known that polymorphisms in the collagen I gene are associated not only with osteoporosis and osteoporotic fracture risk, but also with osteoarthritis. Hypothesis Because collagen I is abundant in ligaments and tendons, the authors hypothesized that collagen I α1 Sp1 polymorphism also was related to the occurrence of cruciate ligament ruptures and shoulder dislocations. Study Design Case-control study; Level of evidence, 3. Methods A total of 358 patients and 325 randomly selected population-based female controls were included in the study. Of the cases, 233 had a cruciate ligament rupture and 126 had had a shoulder dislocation. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) estimated by unconditional logistic regression were used as measures of association. Results Compared with the homozygous SS category, the heterozygous participants displayed a similar risk (OR, 1.06; 95% CI, 0.76–1.49), whereas the ss genotype was underrepresented in the injured population compared with the controls (OR, 0.15; 95% CI, 0.03–0.68). This latter estimate was similar for both cruciate ligament ruptures and shoulder dislocations, and was furthermore not modified by general joint laxity. Conclusion The authors found a substantially decreased risk of these injuries associated with collagen type I α1 Sp1 polymorphism. The study might encourage other investigators to consider further research in the area of genes and soft tissue injuries.


1999 ◽  
Vol 24 (4) ◽  
pp. 395-399 ◽  
Author(s):  
A. M. P. FITZGERALD ◽  
J. J. R. KIRKPATRICK ◽  
I. L. NAYLOR

Histologically, Dupuytren’s disease has been compared to the process of neoplasia because of fibroblast proliferation, recurrence, chromosomal abnormalities and antigenic profiles. However, a comparison of Dupuytren’s tissue with the granulation tissue formed in wound healing could be more valid. Histology reveals similarities in cell types, proliferation, vascularity and collagen morphology. Pharmacologically, both tissues have a similar range of agonist and antagonist responses. Biochemical analysis reveals new collagen synthesis, an increased ratio of type III to type I collagen, and similar changes of the ground substance in both processes. Considering such similarities perhaps it is possible to regard some of the models used for the investigation of wound healing and granulation tissue as the missing experimental “model” for the study of Dupuytren’s disease. Recently great strides have been made in the basic understanding of wound biology, and such a comparison might well provide novel therapeutic options for Dupuytren’s disease.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 877
Author(s):  
Ingrid Zahn ◽  
Daniel David Stöbener ◽  
Marie Weinhart ◽  
Clemens Gögele ◽  
Annette Breier ◽  
...  

Anterior cruciate ligament (ACL) cell sheets combined with biomechanically competent scaffolds might facilitate ACL tissue engineering. Since thermoresponsive polymers allow a rapid enzyme-free detachment of cell sheets, we evaluated the applicability of a thermoresponsive poly(glycidyl ether) (PGE) coating for cruciate ligamentocyte sheet formation and its influence on ligamentocyte phenotype during sheet-mediated colonization of embroidered scaffolds. Ligamentocytes were seeded on surfaces either coated with PGE or without coating. Detached ligamentocyte sheets were cultured separately or wrapped around an embroidered scaffold made of polylactide acid (PLA) and poly(lactic-co-ε-caprolactone) (P(LA-CL)) threads functionalized by gas-phase fluorination and with collagen foam. Ligamentocyte viability, protein and gene expression were determined in sheets detached from surfaces with or without PGE coating, scaffolds seeded with sheets from PGE-coated plates and the respective monolayers. Stable and vital ligamentocyte sheets could be produced within 24 h with both surfaces, but more rapidly with PGE coating. PGE did not affect ligamentocyte phenotype. Scaffolds could be colonized with sheets associated with high cell survival, stable gene expression of ligament-related type I collagen, decorin, tenascin C and Mohawk after 14 d and extracellular matrix (ECM) deposition. PGE coating facilitates ligamentocyte sheet formation, and sheets colonizing the scaffolds displayed a ligament-related phenotype.


2017 ◽  
Vol 67 (3) ◽  
pp. 162-167 ◽  
Author(s):  
Tomasz Latusek ◽  
Leszek Miszczyk ◽  
Grzegorz Gierlach ◽  
Piotr Zając

2005 ◽  
Vol 94 (1) ◽  
pp. 71-75
Author(s):  
M. Forsman ◽  
L. Kallioinen ◽  
M. Kallioinen ◽  
J. Ryhänen

Background: Dupuytren's disease is a chronic inflammatory process which causes contractures of the fingers by shortening and thickening the palmar fascia. During the proliferative phase, fibroblasts transform into myofibroblasts apparently under the influence of several different factors. The disease usually develops slowly, but in some patients it tends to develop aggressively. The pathogenesis of Dupuytren's disease remains unsolved. In this study, we analyzed some histological characteristics that seem to predict rapid recurrence. Material and Methods: 21 patients were divided into two groups. In 11 patients the disease was classified as aggressive because it had recurred within two years after an operation. In 10 cases it was non-aggressive, as no recurrence had been seen. Five control samples were taken from healthy palmar aponeurosis. The differences in cellularity, collagen, Ki-67, MSA, alpha-SMA and tenascin between the specimens were analyzed using immunohistochemistry. Results: Alpha-SMA and Ki-67 were present more often in the aggressive specimens. Immunohistochemical stainings for macrophages and lymphocytes were negative. Conclusion: There may be differences in the histology and/or immunohistochemical appearance of pathological palmar connective tissue cords in aggressive and normal Dupuytren's disease. Further studies are needed to elucidate the pathogenesis of this disease.


2009 ◽  
Vol 315 (20) ◽  
pp. 3574-3586 ◽  
Author(s):  
Linda Vi ◽  
Lucy Feng ◽  
Rebecca D. Zhu ◽  
Yan Wu ◽  
Latha Satish ◽  
...  

Author(s):  
Peter Burge

♦ Dupuytren’s disease is characterised by contracture of a finger resulting from thickening and shortening of the palmar fascia♦ A genetic component to the aetiology is apparent, smoking, alcohol and diabetes can increase the risk♦ The pathogenesis of Dupuytren’s disease remains elusive♦ Non-surgical treatment options include splintage, steroid injection and collagenase injection♦ Surgery cannot cure the disease but can straighten bent digits and minimize recurrence♦ Operative methods can be considered with regards to incision, management of the diseased fascia and closure techniques♦ Operative complications include injury of digital nerves and arteries


2020 ◽  
Vol 45 (5) ◽  
pp. 508-512
Author(s):  
Rafael Sanjuan-Cervero ◽  
Francisco J. Carrera-Hueso ◽  
Manuel Vaquero-Perez ◽  
Daniel Montaner-Alonso

The aim of this study was to determine whether recurrent Dupuytren’s disease after collagenase Clostridium histolyticum treatment differs histologically from recurrence in those treated with fasciectomy. We carried out a prospective cohort study of patients with Dupuytren’s disease who underwent fasciectomy to treat disease recurrence after previous treatment with collagenase Clostridium histolyticum or fasciectomy. The pathologists and statistician were blinded to the previous treatment. Longitudinal biopsy sections were stained with haematoxylin-eosin and the nodular zones were examined. Fifteen patients were studied: nine previously treated with collagenase Clostridium histolyticum and six previously treated with fasciectomy. There were no histological differences between the samples from the two groups of patients. Dupuytren’s disease recurrences after fasciectomy and collagenase Clostridium histolyticum are histologically indistinguishable.


1991 ◽  
Vol 16 (3) ◽  
pp. 267-271 ◽  
Author(s):  
J. G. ANDREW ◽  
S. M. ANDREW ◽  
A. ASH ◽  
B. TURNER

An immunohistochemical study was performed on nodules excised from the palmar fascia of patients with Dupuytren’s contracture. In cellular nodules, antibodies to actin (used as a marker for myofibroblasts), desmin, vimentin, Mac 387 (a macrophage marker) and leucocyte common antigen were used. A correlation was demonstrated between the numbers of macrophages and the presence of myofibroblasts. The presence of myofibroblasts is generally considered to indicate the active stage of the disease. Inflammatory cells other than macrophages were largely absent from the nodules, although lymphocytes were frequent in the tissue around the nodules. Microvascular changes were prominent in the nodules and pericyte proliferation was observed around occluded capillaries. Release of growth factors from macrophages may be important in Dupuytren’s contracture, as is the case in other fibrotic diseases. The possible role of macrophages in the aetiology of Dupuytren’s disease is discussed.


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