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Contractile Properties of Dupuytren’s Fibroblasts: The Effects of TGF-ß
ABSTRACT
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. This study examined 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 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. Fluorescent deconvolutional microscopy showed that exogenous TGF-ß caused markedly altered stress fiber formation in diseased cells compared with control cells.
Dupuytren’s fibroblasts exhibit different phenotypical behavior in three-dimensional culture, but this behavior is most likely not mediated by endogenous differences in TGF-ß signaling.