Matrix and cell phenotype differences in Dupuytren's disease

Area of Science:

• Hand surgery
• Fibroproliferative diseases
• Tissue engineering

Background:

• Dupuytren's disease is a hand and finger fibroproliferative condition.
• It presents with two distinct phenotypes: an initial nodule and a later cord.
• These phenotypes lead to finger contracture.

Purpose of the Study:

• To characterize and compare the distinct phenotypes of Dupuytren's disease.
• To investigate cellular and molecular differences between nodule and cord tissues.
• To understand the mechanisms underlying disease progression.

Main Methods:

• Comparative analysis of matched nodule and cord tissues from ten Dupuytren's patients.
• Cell proliferation assays, immunohistochemistry for macrophages and myofibroblasts (α-SMA).
• Quantitative PCR (qPCR) for collagen gene expression, HPLC for collagen crosslinking, and procollagen processing analysis.

Main Results:

• Nodule tissue exhibited higher cellular proliferation, macrophage (CD68+) infiltration, and myofibroblast (α-SMA+) presence.
• Increased mRNA expression of COL1A1, COL1A2, COL5A1, and COL6A1 was observed in nodules.
• Despite higher mRNA, nodules showed less collagen type I deposition, higher fibronectin, collagen type V, and procollagen 1, suggesting impaired procollagen processing.

Conclusions:

• The nodule represents the active disease site in Dupuytren's disease, characterized by cellular proliferation and myofibroblast activity.
• Differences in collagen type I deposition, despite elevated mRNA and procollagen levels in nodules, indicate a potential role for reduced procollagen processing.
• Cord tissue demonstrates increased collagen type I and higher crosslinking, suggesting a more mature, fibrotic stage.