Collagen production in Dupuytren’s fibrosis: Carpal Tunnel control
Research type
Research Study
Full title
“Collagen (I) homotrimer in age-related fibroses and tissue degeneration: evaluation as a stem cell biomarker - Carpal Tunnel control for collagen production in Dupuytren’s fibrosis”.
IRAS ID
151939
Contact name
Peter Clegg
Contact email
Research summary
Research Summary
This study is part of a larger study funded by the Medical Research Council that aims to identify an abnormal form of collagen that may be responsible for certain age-related diseases. We will test whether this collagen may be associated with stem-cell activity, what determines how much unusual collagen is produced by cells and how it can be controlled. To do this we plan to compare samples from both normal and diseased tissues with stem cells grown in the laboratory. The findings of this study could have broad relevance for understanding age-related musculoskeletal and fibrotic diseases and the function of stem cells in tissue repair and regeneration.
We have preexisting ethical approval for Dupuytren’s disease tissue to analyse abnormal collagen production in tissues with excessive (fibrotic) collagen production, as we already know that some abnormal collagen is produced in Dupuytren’s fibrosis. Control samples for this study will be obtained from patients undergoing carpal tunnel decompression surgery. The control tissue will be a small piece of palmar fascia that would not normally be removed during surgery, but which creates minimal increased risks and adds no more than two minutes to the operating time. Patients over 18 years of age undergoing carpal tunnel decompression will be eligible for inclusion in the study. The surgical procedure will be performed once by an Orthopaedic Surgeon in an NHS Trust. Laboratory analysis of samples will be carried out at the University of Liverpool, Department of Musculoskeletal Biology, Leahurst Site. The study will last for at least 3 years.
Summary of Results
Dupuytren’s (doo-pa-trens) disease is a common condition, affecting up to 1 in 5 of men over 60 years of age and similar numbers of women though often with later onset. Tough fibrous tissue forms in the palm of the hands and occasionally elsewhere in the body, which can lead to contractures of the fingers and thumb. If severe, these can cause significant loss of hand function. There is no known medical cure for the condition. Surgery is used to remove the fibrotic tissue and straighten the contractures, but in some cases the treatment can be unsuccessful. In many cases given time, the tissue can re-form and the problems return.
The study showed that unlike normal tissue, Dupuytren’s samples actively produced an abnormal form of type I collagen, the main protein constituent of fibrotic tissue. There was also active production of fibronectin, a collagen-associated protein, enzymes that can degrade collagen and an enzyme inhibitor. Analysing the protein fingerprint of Dupuytren’s tissue supported activation of TGFβ, a protein controlling fibrosis, but reduction of a controller of the Wnt-signalling pathway that goes awry in Dupuytrens. A subsequent screening approach to identify ways to reduce collagen production by Dupuytren’s cells found a promising inhibitor for future investigation and drug development.
REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
14/NW/0162
Date of REC Opinion
14 Apr 2014
REC opinion
Further Information Favourable Opinion