title: Dupuytren's disease. A model for the mechanism of fibrosis and its modulation by steroids.
abstract: Dupuytren's disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren's tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-beta) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren's disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-beta was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren's tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren's nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-beta stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-beta. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-beta was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible.
authors.affiliation: University Department of Orthopaedics, Western Infirmary, Glasgow, Scotland, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Meek
authors.forename: S
authors.initials: S
authors.lastname: McLellan
authors.forename: J F
authors.initials: JF
authors.lastname: Crossan
mesh_terms: D000328:Adult; D000368:Aged; D004387:Dupuytren Contracture / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005205:Fascia / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1