Abstract
BackgroundDupuytren's disease (DD) is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords) leading to flexion contractures of the fingers and loss of hand function. Although the molecular mechanism of DD is unknown, it has been suggested that transforming growth factor-β2 (TGF-β2) may play an important role in the underlying patho-physiology of the disease. The purpose of this study was to further explore this hypothesis by examining the effects of TGF-β2 on primary cell cultures derived from patient-matched disease and normal palmar fascia tissue using a three-dimensional collagen contraction assay.MethodsFibroblast-populated collagen lattice (FPCL) contraction assays using primary cell cultures derived from diseased and control fascia of the same DD patients were studied in response to exogenous TGF-β2 and neutralizing anti-TGF-β2 antibodies.ResultsContraction of the FPCLs occurred significantly faster and to a greater extent in disease cells compared to control cells. The addition of TGF-β2 enhanced the rate and degree of collagen contraction in a dose-dependent fashion for both control and diseased cells. Neutralizing anti-TGF-β2 antibodies abolished exogenous TGF-β2 stimulated collagen contraction, but did not inhibit the enhanced basal collagen contraction activity of disease FPCL cultures.ConclusionsAlthough exogenous TGF-β2 stimulated both disease and control FPCL contraction, neutralizing anti-TGF-β2 antibodies did not affect the elevated basal collagen contraction activity of disease FPCLs, suggesting that the differences in the collagen contraction activity of control and disease FPCL cultures are not due to differences in the levels of endogenous TGF-β2 activity.
Highlights
Dupuytren's disease (DD) is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions leading to flexion contractures of the fingers and loss of hand function
As described in detail below, we have found that exogenous transforming growth factor-β2 (TGF-β2) could significantly stimulate 'normal' and disease Fibroblast-populated collagen lattice (FPCL) contraction in a dose-dependent manner
We examined the effect of neutralizing anti-TGF-β2 antibodies on the basal collagen contraction activity of primary disease and control FPCL cultures
Summary
Dupuytren's disease (DD) is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords) leading to flexion contractures of the fingers and loss of hand function. Histochemical studies of DD have demonstrated the presence of myofibroblasts [3], increased production of type III collagen [47], and alterations in other extra-cellular matrix proteins including various fibronectin isoforms [8,9,10,11,12,13,14]. These biological features are characteristic of abnormal growth factor regulation, fibrogenic cytokines such as transforming growth factor-beta (TGF-β).
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