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Ann Rheum Dis 63:884-886 doi:10.1136/ard.2003.013748
  • Concise report

Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress synovial fibroblast invasion and cartilage degradation in vivo

  1. C Fiehn1,
  2. E Neumann2,
  3. A Wunder3,
  4. S Krienke1,
  5. S Gay4,
  6. U Müller-Ladner2
  1. 1Department of Haematology, Oncology and Rheumatology, Clinic of Internal Medicine V, University of Heidelberg, Germany
  2. 2Division of Rheumatology and Clinical Immunology, Department of Internal Medicine I, University of Regensburg, Germany
  3. 3Department of Radiochemistry and Radiopharmacology (E0300), German Cancer Research Centre (DKFZ), Heidelberg, Germany
  4. 4WHO Collaborating Centre for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, University of Zürich, Switzerland
  1. Correspondence to:
    Dr U Müller-Ladner
    FJS-Allee 11 Regensburg, 93042 Germany; ulf.mueller-ladnerklinik.uni-regensburg.de
  • Accepted 8 October 2003

Abstract

Objective: To investigate the effect of methotrexate (MTX) and albumin coupled with methotrexate (MTX-HSA) on cartilage invasion and induction of perichondrocytic degradation by rheumatoid arthritis synovial fibroblasts (RA SF) in vivo.

Methods: Human cartilage and RA SF were co-transplanted in three groups of severe combined immunodeficient mice (SCID), which received 1 mg/kg free MTX (n = 9), 1 mg/kg MTX-HSA (n = 6), or 0.9% NaCl (n = 5), respectively, intraperitoneally twice a week. After 4 weeks’ treatment, the mice were killed and the implants analysed histologically.

Results: The control group had a mean (SEM) score for cartilage invasion of RA SF of 2.0 (0.26) and for perichondrocytic cartilage degradation of 1.5 (0.34). In contrast, mice which received MTX showed a significantly reduced invasion (0.78 (0.14), p<0.01) and a reduction in perichondrocytic cartilage degradation scores (0.69 (0.2), p<0.05) in comparison with the control group. Mice treated with MTX-HSA also had significantly reduced scores for RA SF invasion into the cartilage (0.92 (0.41), p<0.05) and for cartilage degradation (0.83 (0.44), p<0.05) compared with controls. The effects of MTX and MTX-HSA were not significantly different between these two groups.

Conclusion: Treatment with MTX or MTX-HSA significantly ameliorates cartilage destruction in the SCID mouse model for human RA.

Footnotes