Dupuytren's contracture is a fibroproliferative disorder characterized by progressive deposition of mature
collagen fibers. In other fibrotic diseases affecting organs such as the liver, lung, heart, and skin,
matrix metalloproteinases (
MMPs) and their natural inhibitors, the tissue inhibitors of
metalloproteinases (TIMPs), play an important role. In this study, serum concentrations of MMP-1, MMP-2, MMP-9,
TIMP-1, and
TIMP-2 were determined in 22 patients (five women and 17 men; average age, 67 +/- 11 years) with
Dupuytren's disease using an
enzyme-linked
immunosorbent assay. Tissue samples were obtained for standard histological and immunohistochemical analyses. Sera and samples of palmar fascia from 20 patients (13 women and seven men; average age, 60 +/- 15 years) who had undergone hand surgery for
carpal tunnel syndrome were used as the control group. Statistical analysis was performed using the Mann-Whitney test. Patients with
Dupuytren's contracture presented with a
TIMP-1 concentration of 437 +/- 160 ng/ml, a significantly higher
TIMP-1 concentration than that seen in the control patients, who had a concentration of 321 +/- 70 ng/ml (p < 0.05). Patients with a proliferative active disease (n = 14) had a significantly higher
TIMP-1 concentration (525 +/- 136 ng/ml) than patients (n = 8) with a
contracture in the late involutional and residual phase (286 +/- 41 ng/ml; p < 0.05). There were no significant differences in the
TIMP-2, MMP-1, MMP-2, and MMP-9 serum concentrations between patients with
palmar fibromatosis and the control group. Patients with
Dupuytren's disease had a significantly lower
MMP-to-TIMP ratio (1.1 +/- 0.3; p < 0.05) than the control group (1.5 +/- 0.35). Patients with an active
palmar fibromatosis presented a significantly (p < 0.05) reduced ratio (1 +/- 0.2) compared with those in later phases (1.4 +/- 0.3).
TIMP-1 and
TIMP-2 could be detected in tissue of patients with
Dupuytren's contracture, with an accumulation in proliferative areas.
MMPs could be detected locally in Dupuytren's tissue in a few patients, with less positive staining than for TIMPs. In the control group, there was just little or no staining for TIMPs and
MMPs. The data indicate that the physiological balance between
MMPs and their natural inhibitors is disturbed in patients with a proliferative active
Dupuytren's disease. The decrease in the systemic
MMP-to-TIMP ratio can cause increased synthesis and deposition of
collagen, leading to
palmar fibromatosis.