Regulating Myofibroblasts in Dupuytren’s Disease

Abstract

Dupuytren’s disease is a common !broproliferative disorder of the palmar fascia. It is named after Baron Guillaume Dupuytren, the surgeon who described the condition in a now famous lecture “La rétraction permanente des doigts” in 1831, despite earlier descriptions by Felix Platter (1680), Henry Cline (1808) and Sir Astley Cooper (1818). The classic description of Dupuytren’s disease progression is the initial appearance of palmar nodules characterized by dense cellularity and cell proliferation, followed by the development of cords. As the disease progresses this phase is followed by a final fibrotic stage leading to relatively less cellular cords and digital contractures resulting in significant impairment of hand function The prevalence of the disease, influenced by the study parameters used, varies according to geographical location and ranges from 0.2% to 56%2. Epidemiology studies indicate that Dupuytren’s disease affects 4-6% of all Caucasians, although it is most common amongst Caucasians of Northern European extraction. In Norway the disease prevalence has been reported reaching 30% in individuals aged over 60 years. Dupuytren’s disease has a familial predisposition, suggesting a genetic link. Previous studies have used DNA microarray and linkage studies, allowing differential analysis of expression of multiple genes. Results have varied and included genes involved in extracellular matrix organisation and metalloproteinases, !bronectin, collagens type III, IV and VI and transforming growth factor. Analysis of subcutaneous fat, fascia and skin overlying Dupuytren’s disease revealed differential gene expression in comparison to control tissue. Recently in a large gene wide association study, a role for the Wnt-signaling pathway in the pathogenesis of Dupuytren’s disease has been suggested. Dupuytren’s has often been associated with various environmental factors. These include smoking, excessive alcohol consumption, diabetes, epilepsy, occupation and trauma. However, their role in the pathogenesis of the disease remains unclear.