Effects of Calcitriol on Fibroblasts Derived from Skin of Scleroderma Patients

Abstract

Background: Scleroderma is a fibrotic disorder of unknown etiology that is characterized by excessive collagen synthesis and its deposition in the skin and various internal organs. Objective: To examine whether an overproduction of extracellular matrix molecules is a result of either increased fibroblast proliferation or increased collagen synthesis. As results of clinical trials with 1,25-dihydroxyvitamin D₃ (calcitriol) have suggested beneficial effect in the treatment of scleroderma patients, the effects of calcitriol on fibroblasts derived from scleroderma and normal skin has been examined as well. Methods: Cultures of fibroblasts were established from biopsies from involved and uninvolved skin of scleroderma patients and from skin of healthy subjects, and compared with respect to proliferation, collagen synthesis and collagen lattice contraction. Results: No significant differences in cell proliferation and in the extent of fibroblast-induced collagen lattice contraction have been found between scleroderma and normal fibroblasts. Morphologically, fibroblasts derived from scleroderma patients exhibited a disorganized growth pattern in a monolayer culture in contrast to normal fibroblasts. Collagen synthesis tends to be higher in scleroderma fibroblasts as compared with controls. Calcitriol exerted an antiproliferative and antisynthetic effect on fibroblasts, which, however, did not discriminate healthy fibroblasts from fibroblasts derived from involved or uninvolved scleroderma plaques. Conclusions: Our findings suggest that collagen accumulation may not result from increased proliferation or altered dynamic properties of fibroblasts in a scleroderma lesion but from increased collagen biosynthesis. We additionally found that calcitriol does not selectively affect scleroderma fibroblasts.