Effects of methotrexate on glycosaminoglycan production by scleroderma fibroblasts in culture.
OBJECTIVE
To determine the effects of increasing concentrations of methotrexate on the proliferation and glycosaminoglycan (GAG) synthesis of cultured dermal fibroblasts from patients with scleroderma.


METHODS
Cultured dermal fibroblasts from nine patients with scleroderma and nine normal volunteers were grown for 72 hours in media containing various concentrations of methotrexate. The GAG synthesis in each cell was measured after incubating the fibroblasts with [3H]glucosamine and [35S]sulphate.


RESULTS
A negative correlation was found between the concentration of methotrexate and numbers of fibroblasts from patients with scleroderma and normal controls. A positive correlation was found between GAG synthesis in each cell, as measured by [3H]glucosamine and [35S]sulphate incorporation, and increasing methotrexate concentrations in fibroblasts from patients with scleroderma and normal controls.


CONCLUSIONS
These data indicate increased GAG synthesis in scleroderma and normal fibroblasts with increasing concentrations of methotrexate. Therefore the reported beneficial effect of methotrexate on skin fibrosis in scleroderma is most probably not the result of direct inhibition of GAG synthesis by fibroblasts.
van den Hoogen
F H
FH
Department of Rheumatology, University Hospital, Nijmegen, The Netherlands.
van der Kraan
P M
PM
Boerbooms
A M
AM
van den Berg
W B
WB
van Lier
H J
HJ
van de Putte
L B
LB
D000328:Adult; D000368:Aged; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology*
D006025:Glycosaminoglycans; D008727:Methotrexate