title: Enhanced Dupuytren's disease fibroblast populated collagen lattice contraction is independent of endogenous active TGF-beta2.
abstract: BACKGROUND
  Dupuytren's disease (DD) is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords) leading to flexion contractures of the fingers and loss of hand function. Although the molecular mechanism of DD is unknown, it has been suggested that transforming growth factor-beta2 (TGF-beta2) may play an important role in the underlying patho-physiology of the disease. The purpose of this study was to further explore this hypothesis by examining the effects of TGF-beta2 on primary cell cultures derived from patient-matched disease and normal palmar fascia tissue using a three-dimensional collagen contraction assay.
  
  
  METHODS
  Fibroblast-populated collagen lattice (FPCL) contraction assays using primary cell cultures derived from diseased and control fascia of the same DD patients were studied in response to exogenous TGF-beta2 and neutralizing anti-TGF-beta2 antibodies.
  
  
  RESULTS
  Contraction of the FPCLs occurred significantly faster and to a greater extent in disease cells compared to control cells. The addition of TGF-beta2 enhanced the rate and degree of collagen contraction in a dose-dependent fashion for both control and diseased cells. Neutralizing anti-TGF-beta2 antibodies abolished exogenous TGF-beta2 stimulated collagen contraction, but did not inhibit the enhanced basal collagen contraction activity of disease FPCL cultures.
  
  
  CONCLUSIONS
  Although exogenous TGF-beta2 stimulated both disease and control FPCL contraction, neutralizing anti-TGF-beta2 antibodies did not affect the elevated basal collagen contraction activity of disease FPCLs, suggesting that the differences in the collagen contraction activity of control and disease FPCL cultures are not due to differences in the levels of endogenous TGF-beta2 activity.
authors.affiliation: Department of Surgery, The University of Western Ontario, London, Ontario, Canada. rtse@uwo.ca <rtse@uwo.ca>
authors.forename: Raymond
authors.initials: R
authors.lastname: Tse
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Howard
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Bing Siang
authors.initials: BS
authors.lastname: Gan
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004387:Dupuytren Contracture / Q000503:physiopathology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D053781:Transforming Growth Factor beta2
chemical_list: D000888:Antibodies, Anti-Idiotypic; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D003094:Collagen