title: Elevated levels of beta-catenin and fibronectin in three-dimensional collagen cultures of Dupuytren's disease cells are regulated by tension in vitro.
abstract: BACKGROUND
  Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in the development of scar-like, collagen-rich disease cords within specific palmar fascia bands. Although the molecular pathology of DD is unknown, recent evidence suggests that beta-catenin may play a role. In this study, collagen matrix cultures of primary disease fibroblasts show enhanced contraction and isometric tension-dependent changes in beta-catenin and fibronectin levels.
  
  
  METHODS
  Western blots of beta-catenin and fibronectin levels were determined for control and disease primary cell cultures grown within stressed- and attached-collagen matrices. Collagen contraction was quantified, and immunocytochemistry analysis of filamentous actin performed.
  
  
  RESULTS
  Disease cells exhibited enhanced collagen contraction activity compared to control cells. Alterations in isometric tension of collagen matrices triggered dramatic changes in beta-catenin and fibronectin levels, including a transient increase in beta-catenin levels within disease cells, while fibronectin levels steadily decreased to levels below those seen in normal cell cultures. In contrast, both fibronectin and beta-catenin levels increased in attached collagen-matrix cultures of disease cells, while control cultures showed only increases in fibronectin levels. Immunocytochemistry analysis also revealed extensive filamentous actin networks in disease cells, and enhanced attachment and spreading of disease cell in collagen matrices.
  
  
  CONCLUSIONS
  Three-dimensional collagen matrix cultures of primary disease cell lines are more contractile and express a more extensive filamentous actin network than patient-matched control cultures. The elevated levels of beta-catenin and Fn seen in collagen matrix cultures of disease fibroblasts can be regulated by changes in isometric tension.
authors.affiliation: Department of Surgery, University of Western Ontario, London, Ontario, Canada. jhoward@lri.sjhc.london.on.ca
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Howard
authors.forename: Vincenzo M
authors.initials: VM
authors.lastname: Varallo
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Ross
authors.forename: James H
authors.initials: JH
authors.lastname: Roth
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Faber
authors.forename: Benjamin
authors.initials: B
authors.lastname: Alman
authors.forename: Bing Siang
authors.initials: BS
authors.lastname: Gan
mesh_terms: D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004387:Dupuytren Contracture / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D015534:Trans-Activators; D051176:beta Catenin; D003094:Collagen