Abstract
BackgroundDupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures. Increased cellular β-catenin levels have been identified as characteristic of this disease. As Wnts are the most widely recognized upstream regulators of cellular β-catenin accumulation, we have examined Wnt gene expression in surgical specimens and in DD-derived primary cell cultures grown in two-dimensional monolayer culture or in three-dimensional FPCL collagen lattice cultures.ResultsThe Wnt expression profile of patient-matched DD and unaffected control palmar fascia tissue was determined by a variety of complimentary methods; Affymetrix Microarray analysis, specific Wnt and degenerative primer-based Reverse Transcriptase (RT)-PCR, and Real Time PCR. Microarray analysis identified 13 Wnts associated with DD and control tissues. Degenerate Wnt RT-PCR analysis identified Wnts 10b and 11, and to a lesser extent 5a and 9a, as the major Wnt family members expressed in our patient samples. Competitive RT-PCR analysis identified significant differences between the levels of expression of Wnts 9a, 10b and 11 in tissue samples and in primary cell cultures grown as monolayer or in FPCL, where the mRNA levels in tissue > FPCL cultures > monolayer cultures. Real Time PCR data confirmed the down-regulation of Wnt 11 mRNA in DD while Wnt 10b, the most frequently isolated Wnt in DD and control palmar fascia, displayed widely variable expression between the methods of analysis.ConclusionThese data indicate that changes in Wnt expression per se are unlikely to be the cause of the observed dysregulation of β-catenin expression in DD.
Highlights
Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures
These data indicate that changes in Wnt expression per se are unlikely to be the cause of the observed dysregulation of β-catenin expression in DD
Affymetrix microarray analysis The primary goal of this project was to determine the expression status of all Wnts expressed in DD and control palmar fascia (PF)
Summary
Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures. Increased cellular β-catenin levels have been identified as characteristic of this disease. Β-Catenin plays both a structural role, as a cadherin-binding protein in cell adhesion junctions [10,11], and a signalling role, as part of the Wnt/β-catenin pathway [12]. The Wnt/Fz/LRP complex triggers a cascade of signalling events that lead to the stabilization of a 'cadherin-free' cytoplasmic pool of β-catenin. The cytoplasmic accumulation of β-catenin results in its translocation to the nucleus where it functions as a transcriptional activator for members of the lymphoid enhancer factor/Tcell factor (Lef/Tcf) family of DNA binding proteins [21,22]
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