Abstract

Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM) and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues—Dupuytren's diseased contracture cords (DDC), palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF), and normal forehand fascia (NFF). Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA), fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered.

Highlights

  • Dupuytren’s disease (DD) is a proliferative disorder affecting the palm of the hands that is characterized by an alteration of the cells and extracellular matrix (ECM) of the palm fascia

  • This finding implies that NPF cells could share important similarities with diseased contracture cords (DDC) cells, suggesting that NPF tissues could not be normal from a gene expression standpoint even though these are apparently clinically unaffected

  • To shed light on this issue, we first quantified the number of cells present in each tissue and determined the percentage of cells that were positive for smooth muscle actin, a marker of myofibroblasts

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Summary

Introduction

Dupuytren’s disease (DD) is a proliferative disorder affecting the palm of the hands that is characterized by an alteration of the cells and extracellular matrix (ECM) of the palm fascia. This alteration may lead to an irreducible and progressively disabling flexion and contracture of the fingers, with loss of function and deformity of the hand [1]. A comprehensive histological and genetic analysis of the fibrillar and non-fibrillar components of the ECM and the normal palm fascia has not been performed to the date, previous studies have identified alterations of type I and type III collagens, fibronectin, laminin and other ECM components in DD [6], along with an important disregulation of several genes encoding proteins in the WNTsignaling pathway [7]

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