Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress synovial fibroblast invasion and cartilage degradation in vivo
- 1Department of Haematology, Oncology and Rheumatology, Clinic of Internal Medicine V, University of Heidelberg, Germany
- 2Division of Rheumatology and Clinical Immunology, Department of Internal Medicine I, University of Regensburg, Germany
- 3Department of Radiochemistry and Radiopharmacology (E0300), German Cancer Research Centre (DKFZ), Heidelberg, Germany
- 4WHO Collaborating Centre for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, University of Zürich, Switzerland
- Correspondence to:
Dr U Müller-Ladner
FJS-Allee 11 Regensburg, 93042 Germany;
- Accepted 8 October 2003
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.
- CIA, collagen induced arthritis
- HAS, human serum albumin
- IL, interleukin
- MTX, methotrexate
- RA, rheumatoid arthritis
- SCID, severe combined immunodeficient
- SF, synovial fibroblasts