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


CONCLUSIONS
Treatment with MTX or MTX-HSA significantly ameliorates cartilage destruction in the SCID mouse model for human RA.
Fiehn
C
C
Department of Haematology, Oncology and Rheumatology, Clinic of Internal Medicine V, University of Heidelberg, Germany.
Neumann
E
E
Wunder
A
A
Krienke
S
S
Gay
S
S
Müller-Ladner
U
U
D000418:Albumins / Q000627:therapeutic use*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D002356:Cartilage / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008727:Methotrexate / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D012709:Serum Albumin / Q000627:therapeutic use; D013583:Synovial Membrane / Q000473:pathology*
D000418:Albumins; D007166:Immunosuppressive Agents; D012709:Serum Albumin; C040811:methotrexate-serum albumin; D008727:Methotrexate