The 2004 Annual Meeting (January 14-20, 2004) of OASYS_NEW

Not yet assigned to a slot - 4:40 AM

Contractile properties of Dupuytren’s fibroblasts: the effects of TGF-ß

Tse R, Howard JC, and Gan BS. University of Western Ontario, Hand and Upper Limb Centre, St. Joseph's Health Centre, 268 Grosvenor Street, London, ON, Canada

Dupuytren’s disease is a fibroproliferative disorder of the palmar fascia with no definitive cause.  The search for its etiology has shifted from clinical association to molecular biology.  Transforming growth factor beta (TGF-ß), an important cytokine involved in wound healing, has been implicated in the pathogenesis of Dupuytren’s contracture.  The purpose of this study was to examine the effects of exogenous TGF-ß on cultured Dupuytren’s contracture fibroblasts in a collagen matrix.  In diseased cells, collagen gel contraction was significantly faster and to a greater extent than in control cells.  The addition of TGF-ß enhanced the rate and degree of contraction in a dose-dependent fashion for both control and diseased cells.  Blocking antibodies to TGF-ß abolished the enhancement of contraction by exogenous TGF-ß, however, addition of the blocking antibodies alone had no effect on basal contraction rates. Interestingly, fluorescent deconvolutional microscopy showed that exogenous TGF-ß caused markedly altered stress fiber formation in diseased cells compared to control cells.  We conclude that Dupuytren’s fibroblasts exhibit different phenotypical behavior in three-dimensional culture, but that this different behavior is most likely not mediated by endogenous differences in TGF-β signaling.