Type-1 Collagen differentially alters beta-catenin accumulation in primary Dupuytren's Disease cord and adjacent palmar fascia cells.
BACKGROUND
Dupuytren's Disease (DD) is a debilitating contractile fibrosis of the palmar fascia characterised by excess collagen deposition, contractile myofibroblast development, increased transforming growth factor-beta levels and beta-catenin accumulation. The aim of this study was to determine if a collagen-enriched environment, similar to in vivo conditions, altered beta-catenin accumulation by primary DD cells in the presence or absence of transforming growth factor-beta.


METHODS
Primary DD and patient matched, phenotypically normal palmar fascia (PF) cells were cultured in the presence or absence of type-1 collagen and transforming growth factor-beta1. beta-catenin and alpha-smooth muscle actin levels were assessed by western immunoblotting and immunofluorescence microscopy.


RESULTS
DD cells display a rapid depletion of cellular beta-catenin not evident in patient-matched PF cells. This effect was not evident in either cell type when cultured in the absence of type-1 collagen. Exogenous addition of transforming growth factor-beta1 to DD cells in collagen culture negates the loss of beta-catenin accumulation. Transforming growth factor-beta1-induced alpha-smooth muscle actin, a marker of myofibroblast differentiation, is attenuated by the inclusion of type-1 collagen in cultures of DD and PF cells.


CONCLUSIONS
Our findings implicate type-1 collagen as a previously unrecognized regulator of beta-catenin accumulation and a modifier of TGF-beta1 signaling specifically in primary DD cells. These data have implications for current treatment modalities as well as the design of in vitro models for research into the molecular mechanisms of DD.
Vi
Linda
L
Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, Lawson Health Research Institute, London, Canada. lvi@uwo.ca
Njarlangattil
Anna
A
Wu
Yan
Y
Gan
Bing Siang
BS
O'Gorman
David B
DB
D000199:Actins / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D004387:Dupuytren Contracture / Q000378:metabolism* / Q000473:pathology; D005205:Fascia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D000199:Actins; C495270:CTNNB1 protein, human; D024042:Collagen Type I; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D051176:beta Catenin