Keywords:
INVASION
;
Germany
;
human
;
IN-VIVO
;
MODEL
;
VIVO
;
MICE
;
GENE-TRANSFER
;
REDUCTION
;
INDUCTION
;
CONTRAST
;
fibroblasts
;
treatment
;
MOUSE
;
score
;
IMMUNODEFICIENT MICE
;
DEGRADATION
;
MOUSE MODEL
;
METHOTREXATE
;
BEARING RATS
;
albumin
;
fibroblast
;
rheumatoid arthritis
;
RHEUMATOID-ARTHRITIS
;
CYTOKINE INHIBITORS
;
DESTRUCTION
;
INTERLEUKIN-1
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
Type of Publication:
Journal article published
Deep Link:
http://www.dkfz.de/cgi-bin/sel?http://www.dkfz.de/PublicationManager/Show/ShowJournal.aspx%3fpublishedId=1079
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