Methotrexate (MTX) and Albumin Coupled With MTX (MTX-HSA) Suppress Synovial Fibroblast Invasion and Cartilage Degradation in Vivo

Ann Rheum Dis. 2004 Jul;63(7):884-6. doi: 10.1136/ard.2003.013748.

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.

MeSH terms

  • Albumins / therapeutic use*
  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Cartilage / pathology*
  • Cell Movement / drug effects
  • Drug Therapy, Combination
  • Female
  • Fibroblasts / pathology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Methotrexate / therapeutic use*
  • Mice
  • Mice, SCID
  • Models, Animal
  • Serum Albumin / therapeutic use
  • Synovial Membrane / pathology*

Substances

  • Albumins
  • Immunosuppressive Agents
  • Serum Albumin
  • methotrexate-serum albumin
  • Methotrexate