RESEARCH - MTX and MTX-HSA suppress synovial fibroblast invasion and cartilage degradation in vivo

August 30, 2004

Ann Rheum Dis. 2004 Jul;63(7):884-6.

Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress

synovial fibroblast invasion and cartilage degradation in vivo.

Fiehn C, Neumann E, Wunder A, Krienke S, Gay S, Muller-Ladner U.

Department of Haematology, Oncology and Rheumatology, Clinic of Internal

Medicine V, University of Heidelberg, Germany.

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.

PMID: 15194591

5194591 & dopt=Abstract

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Mayo Clinic in Rochester

s Hopkins Medicine

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