Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1993 Oct;52(10):758–761. doi: 10.1136/ard.52.10.758

Effects of methotrexate on glycosaminoglycan production by scleroderma fibroblasts in culture.

F H van den Hoogen 1, P M van der Kraan 1, A M Boerbooms 1, W B van den Berg 1, H J van Lier 1, L B van de Putte 1
PMCID: PMC1005174  PMID: 8257212

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.

Full text

PDF
758

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bashey R. I., Millan A., Jimenez S. A. Increased biosynthesis of glycosaminoglycans by scleroderma fibroblasts in culture. Arthritis Rheum. 1984 Sep;27(9):1040–1045. doi: 10.1002/art.1780270911. [DOI] [PubMed] [Google Scholar]
  2. Cabral A., Castor C. W. Connective tissue activation. XXVII. The behavior of skin fibroblasts from patients with scleroderma. Arthritis Rheum. 1983 Nov;26(11):1362–1369. doi: 10.1002/art.1780261109. [DOI] [PubMed] [Google Scholar]
  3. Jeurissen M. E., Boerbooms A. M., van de Putte L. B., Doesburg W. H., Mulder J., Rasker J. J., Kruijsen M. W., Haverman J. F., van Beusekom H. J., Muller W. H. Methotrexate versus azathioprine in the treatment of rheumatoid arthritis. A forty-eight-week randomized, double-blind trial. Arthritis Rheum. 1991 Aug;34(8):961–972. doi: 10.1002/art.1780340805. [DOI] [PubMed] [Google Scholar]
  4. LeRoy E. C. Increased collagen synthesis by scleroderma skin fibroblasts in vitro: a possible defect in the regulation or activation of the scleroderma fibroblast. J Clin Invest. 1974 Oct;54(4):880–889. doi: 10.1172/JCI107827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Metzger A. L., Bohan A., Goldberg L. S., Bluestone R., Pearson C. M. Polymyositis and dermatomyositis: combined methotrexate and corticosteroid therapy. Ann Intern Med. 1974 Aug;81(2):182–189. doi: 10.7326/0003-4819-81-2-182. [DOI] [PubMed] [Google Scholar]
  6. Needleman B. W., Ordonez J. V., Taramelli D., Alms W., Gayer K., Choi J. In vitro identification of a subpopulation of fibroblasts that produces high levels of collagen in scleroderma patients. Arthritis Rheum. 1990 Jun;33(6):842–852. doi: 10.1002/art.1780330611. [DOI] [PubMed] [Google Scholar]
  7. Schwartz P. M., Barnett S. K., Atillasoy E. S., Milstone L. M. Methotrexate induces differentiation of human keratinocytes. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):594–598. doi: 10.1073/pnas.89.2.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Segal R., Yaron M., Tartakovsky B. Methotrexate: mechanism of action in rheumatoid arthritis. Semin Arthritis Rheum. 1990 Dec;20(3):190–200. doi: 10.1016/0049-0172(90)90060-s. [DOI] [PubMed] [Google Scholar]
  9. Uitto J., Bauer E. A., Eisen A. Z. Scleroderma: increased biosynthesis of triple-helical type I and type III procollagens associated with unaltered expression of collagenase by skin fibroblasts in culture. J Clin Invest. 1979 Oct;64(4):921–930. doi: 10.1172/JCI109558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Weinblatt M. E., Coblyn J. S., Fox D. A., Fraser P. A., Holdsworth D. E., Glass D. N., Trentham D. E. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med. 1985 Mar 28;312(13):818–822. doi: 10.1056/NEJM198503283121303. [DOI] [PubMed] [Google Scholar]
  11. van den Hoogen F. H., Boerbooms A. M., van de Putte L. B., Rasker J. J., van Venrooij W. J. Low dose methotrexate treatment in systemic sclerosis. J Rheumatol. 1991 Nov;18(11):1763–1764. [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES