Epidermal Paracrine Signals May Regulate Dupuytren Contracture Myofibroblasts.

Dupuytren contracture (DC), frequently treated by hand surgeons, is a common, benign fibrotic condition driven by myofibroblasts causing contractures and stimulating excess collagen production within DC nodules. Within DC cords, myofibroblasts are present in reduced numbers and appear inactive. We hypothesized that keratinocytes differentially express local paracrine signals overlying the DC nodules and cords that induce changes in myofibroblasts within DC lesions.

An Albany Medical Center institutional review board-approved study (#2330) was conducted using tissue obtained from 6 patients undergoing fasciectomy for DC. The samples consisted of adherent skin and underlying diseased fascia; these were analyzed using trichrome staining and standard immunohistochemistry to detect the presence of α-smooth muscle actin and cyclo-oxygenase-2 (COX-2). We observed that within the DC cords, there was abundant fibrous tissue, with reduced numbers of α-smooth muscle actin-positive myofibroblasts that expressed COX-2. Taken together, these data suggested a potentially waning inflammatory local microenvironment because COX-2 induction has been demonstrated to engage in a negative, autocrine feedback loop that restrains the myofibroblast phenotype (Fig.).,

Figure

The adherent skin and underlying diseased fascia excised from a patient undergoing a limited palmodigital fasciectomy. A (Hematoxylin-eosin stain; magnification × 13.4). The excised tissue demonstrates nodules of fibroblasts with bland nuclei and surrounding collagen depositions. B (Trichrome stain; magnification × 13.6). Collagenous deposition is highlighted within the diseased fascia. C (COX-2 immunostain; magnification × 13.4). Cytoplasmic staining of fibroblasts is demonstrated. D (SMA-α immunostain; magnification × 10). The deposition of actin within collagen bundles is demonstrated. E (SMA-α immunostain; magnification × 30). The deposition of actin within collagen bundles is demonstrated. F (COX-2 immunostain; magnification × 30). The cytoplasmic staining of fibroblasts is demonstrated. SMA-α, α-smooth muscle actin.

Our findings, although preliminary, are consistent with a potential role of epidermal keratinocytes in tempering the profibrotic myofibroblast phenotype in DC. Paracrine signaling from the epidermis to DC myofibroblasts is currently an understudied area that may provide new therapeutic approaches in which factors inducing fibroblast COX-2 or resulting prostanoids in DC lesions may be beneficial.