title: Matrix and cell phenotype differences in Dupuytren's disease.
abstract: BACKGROUND
  Dupuytren'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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Marike M
authors.initials: MM
authors.lastname: van Beuge
authors.affiliation: Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands ; Department of Plastic Surgery, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Evert-Jan P M
authors.initials: EJ
authors.lastname: Ten Dam
authors.affiliation: Department of Plastic Surgery, Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Paul M N
authors.initials: PM
authors.lastname: Werker
authors.affiliation: Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Bank
keywords: Collagen biosynthesis; Dupuytren’s disease; Fibroblast; PCOLCE2