Matrix and cell phenotype differences in Dupuytren's disease.

Marike M Van Beuge,Ruud A Bank,Paul M N Werker,Evert-Jan P M Ten Dam

doi:10.1186/s13069-016-0046-0

Marike M Van Beuge, Ruud A Bank + Show 2 more

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https://doi.org/10.1186/s13069-016-0046-0

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Abstract

BackgroundDupuytren’s disease is a fibroproliferative disease of the hand and fingers, which usually manifests as two different phenotypes within the same patient. The disease first causes a nodule in the palm of the hand, while later, a cord develops, causing contracture of the fingers.ResultsWe set out to characterize the two phenotypes by comparing matched cord and nodule tissue from ten Dupuytren’s patients. We found that nodule tissue contained more proliferating cells, CD68-positive macrophages and α-smooth muscle actin (α-SMA)-positive myofibroblastic cells. qPCR analysis showed an increased expression of COL1A1, COL1A2, COL5A1, and COL6A1 in nodule tissue compared to cord tissue. Immunohistochemistry showed less deposition of collagen type I in nodules, although they contained more fibronectin, collagen type V, and procollagen 1. Lower collagen levels in nodule were confirmed by HPLC measurements of the Hyp/Pro ratio. PCOLCE2, an activator of BMP1, the main enzyme cleaving the C-terminal pro-peptide from procollagen, was also reduced in nodule. Cord tissue not only contained more collagen I, but also higher levels of hydroxylysylpyridinoline and lysylpyridinoline residues per triple helix, indicating more crosslinks.ConclusionsOur results clearly show that in Dupuytren’s disease, the nodule is the active disease unit, although it does not have the highest collagen protein levels. The difference in collagen type I deposition compared to mRNA levels and procollagen 1 levels may be connected to a decrease in procollagen processing.Electronic supplementary materialThe online version of this article (doi:10.1186/s13069-016-0046-0) contains supplementary material, which is available to authorized users.

Highlights

Dupuytren’s disease is a fibroproliferative disease of the hand and fingers, which usually manifests as two different phenotypes within the same patient
Staining for Ki-67, which is expressed in the nuclei of proliferating cells, showed that the number of proliferating cells was significantly higher in nodule tissue compared to cord tissue of the same patients (Fig. 1a)
Extracellular matrix production To study the differences in the production of extracellular matrix between cord and nodule of Dupuytren’s patients, we first performed a gene expression analysis on extracellular matrix components and biosynthesis molecules

Summary

Introduction

Dupuytren’s disease is a fibroproliferative disease of the hand and fingers, which usually manifests as two different phenotypes within the same patient. Any fibrotic process is an interplay between cells and matrix, with the matrix influencing cell proliferation, adhesion, and migration, and the cells influencing matrix composition and crosslinking [1] This process is the ultimate consequence of a range of insults and can occur in virtually all organs of the body, with many differences and similarities between the organs. Dupuytren’s disease is a very common (prevalence 0.6 to 31.6 % [3]) fibroproliferative disease of the hand and fingers, which generally starts with the formation of a nodule in the palm of the hand, and progresses with the formation of a cord towards the fingers, which causes eventual contraction and the inability to extend the fingers These two phenotypes commonly occur together in the same patient [4]

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