title: Effects of methotrexate on glycosaminoglycan production by scleroderma fibroblasts in culture.
abstract: 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.
authors.affiliation: Department of Rheumatology, University Hospital, Nijmegen, The Netherlands.
authors.forename: F H
authors.initials: FH
authors.lastname: van den Hoogen
authors.forename: P M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: A M
authors.initials: AM
authors.lastname: Boerbooms
authors.forename: W B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: H J
authors.initials: HJ
authors.lastname: van Lier
authors.forename: L B
authors.initials: LB
authors.lastname: van de Putte
mesh_terms: 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*
chemical_list: D006025:Glycosaminoglycans; D008727:Methotrexate