Wednesday, October 13, 2004 - 9:55 AM

The Effects of Transforming Growth Factor-Beta on Cultured Dupuytren’s Fibroblasts in a Collagen Matrix

Raymond Tse, MD, Bing Siang Gan, MD, PHD, FRCSC, and Jeffrey Howard, PhD.

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-β), 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-β 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-β enhanced the rate and degree of contraction in a dose-dependent fashion for both control and diseased cells. Blocking antibodies to TGF-β abolished the enhancement of contraction by exogenous TGF-β however, addition of the blocking antibodies alone had no effect on basal contraction rates. Interestingly, fluorescent deconvolutional microscopy showed that exogenous TGF-β caused markedly altered stress fiber formation in diseased cells compared to control cells. We conclude that Dupuytren's fibroblasts exhibit different phenotypical behaviour in three-dimensional culture, but that this different behaviour is most likely not mediated by endogenous differences in TGF-β signaling.
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