Expression of matrix metalloproteinases and their inhibitors in cords and nodules of patients with Dupuytren’s disease

Abstract

Dupuytren's disease is a fibroproliferative disorder characterized by thickening of the palmar fascia. Several studies indicate that MMPs and TIMPs may play a key role in the onset or progression of Dupuytren's disease and related disorders. In this study, we used a quantitative reverse-transcription PCR methodology to profile the expression of TIMP1, TIMP2, MMP2, and MMP9 in nodule and cord tissue from patients with Dupuytren's disease and compared this with normal palmar fascia taken at carpal tunnel release. Tissue from patients with Dupuytren's disease was taken at fasciectomy (n = 30; 23 men and 7 women; average age 61.3 +/- 9.5 years). Samples were divided into regions of nodule and cord according to gross morphology. Normal fascia was taken from patients without Dupuytren's contracture who had carpal tunnel release (n = 30; 14 men and 16 women; average age 63 +/- 11 years). Expression of mRNA was calculated using a relative quantification method (Pfaffl). Statistical analysis was performed using the Mann-Whitney test. The level of significance was considered to be P < 0.05. In comparison to normal fascia, the cords and nodules from patients with Dupuytren's disease showed significant upregulation for TIMP1 and TIMP2 (P < 0.05). The expression of TIMP1 was significantly higher in nodules in comparison to cord tissue (P < 0.05). The expression of MMP2 was significantly upregulated in tissue of patients with Dupuytren's contracture in comparison to normal tissue (P < 0.05). The expression of MMP2 was significantly higher in nodules in comparison to cord tissue (P < 0.05). There was no significant difference in the relative expression of MMP9 in nodules and cord tissue of patients with Dupuytren's contracture in comparison to normal fascia from patients with carpal tunnel syndrome. The balance between MMPs and their natural inhibitors is disturbed in patients with Dupuytren's disease. The decrease in MMP-to-TIMP expression can cause increased synthesis and deposition of collagen, leading to palmar fibromatosis. The high expression of MMP2 may represent an unsuccessful attempt to reduce collagen deposition. In the future, a treatment that downregulates TIMPs but increases the activity of MMPs may be an appropriate therapy for Dupuytren's disease.