Effects of calcitriol on fibroblasts derived from skin of scleroderma patients.
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 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.
Department of Dermatology, University Hospital Leiden, The Netherlands.
E
E
Boelsma
S
S
Pavel
M
M
Ponec
D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000494:pharmacology; D001706:Biopsy; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000378:metabolism; D012594:Scleroderma, Localized / Q000473:pathology / Q000503:physiopathology*; D012595:Scleroderma, Systemic / Q000473:pathology / Q000503:physiopathology*; D012867:Skin / Q000187:drug effects* / Q000473:pathology
D002250:Carbon Radioisotopes; D003094:Collagen; D011392:Proline; D002117:Calcitriol; D001205:Ascorbic Acid