The role of an MMP inhibitor in the regulation of mechanical tension by Dupuytren's disease fibroblasts.
Mechanical tension and contracture are two related facets of tissue biology. This study assessed the effect of ilomastat, a broad-spectrum matrix metalloprotease (MMP) inhibitor, on generation of tension by Dupuytren's disease fibroblasts. Nodule and cord-derived fibroblasts were isolated from five patients with Dupuytren's disease; flexor retinaculum acted as the control. A culture force monitor (CFM) provided an in vitro model of tissue organization to assess development of mechanical tension, lattice contraction and spatial remodelling by fibroblasts. Responses to ilomastat were compared to treatment with a control peptide. Nodule and cord-derived fibroblasts exhibited a two-fold increase in tension compared with flexor retinaculum. Ilomastat significantly inhibited development of tension by nodule and cord but not flexor retinaculum derived fibroblasts at 100 microM. These results imply that MMP activity mediates regulation of tensile strength by Dupuytren's disease fibroblasts and may be an important therapeutic target in patients with Dupuytren's disease.
RAFT Institute of Plastic and Reconstructive Surgery, Mount Vernon Hospital, Northwood, UK. willtownley@hotmail.com
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Townley
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Cambrey
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Khaw
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Grobbelaar
D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D004387:Dupuytren Contracture / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids; D007211:Indoles / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D; C119203:ilomastat