EFFECTS OF CALCITRIOL ON FIBROBLASTS DERIVED FROM SKIN OF SCLERODERMAPATIENTS

Background: Scleroderma is a fibrotic disorder of unknown etiology tha t 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 ei ther increased fibroblast proliferation or increased collagen synthesi s. As results of clinical trials with 1,25-dihydroxyvitamin D-3 (calci triol) have suggested beneficial effect in the treatment of scleroderm a patients, the effects of calcitriol on fibroblasts derived from scle roderma and normal skin has been examined as well. Methods: Cultures o f fibroblasts were established from biopsies from involved and uninvol ved skin of scleroderma patients and from skin of healthy subjects, an d compared with respect to proliferation, collagen synthesis and colla gen lattice contraction. Results: No significant differences in cell p roliferation and in the extent of fibroblast-induced collagen lattice contraction have been found between scleroderma and normal fibroblasts . Morphologically, fibroblasts derived from scleroderma patients exhib ited a disorganized growth pattern in a monolayer culture in contrast to normal fibroblasts. Collagen synthesis tends to be higher in sclero derma fibroblasts as compared with controls. Calcitriol exerted an ant iproliferative and antisynthetic effect on fibroblasts, which, however , did not discriminate healthy fibroblasts from fibroblasts derived fr om involved or uninvolved scleroderma plaques. Conclusions: Our findin gs suggest that collagen accumulation may not result from increased pr oliferation or altered dynamic properties of fibroblasts in a sclerode rma lesion but from increased collagen biosynthesis. We additionally f ound that calcitriol does not selectively affect scleroderma fibroblas ts.