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- Title
Combination of MTX and LEF attenuates inflammatory bone erosion by down-regulation of receptor activator of NF-kB ligand and interleukin-17 in type II collagen-induced arthritis rats.
- Authors
Yao, Yao; Ding, Cong-zhu; Fang, Yun
- Abstract
The objectives of this study were to determine the effect of combination of methotrexate (MTX) and leflunomide (LEF) on type II collagen-induced arthritis rats and its mechanism. Curative effect was confirmed on CIA rats, which were randomized and divided into model, MTX, LEF and MTX + LEF group. Weights and joint swelling scores of rats were recorded. Interleukin (IL)-17, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) concentration in serum were determined by ELISA. H&E dyeing of joint was used to estimate the inflammation and osteoclasia extent. The mechanism was investigated through fibroblast-like synoviocytes isolated from RA patients. The effect of MTX and LEF on cell viability, and RANKL and OPG expression were indicated through MTT and RT-PCR analysis, respectively. Combination therapy would be effective in treating CIA rats. Joint swelling scores and IL-17 and RANKL level in serum were decreased obviously ( P < 0.05), while OPG level was elevated ( P < 0.05). Anti-inflammatory and anti-osteoclasia effect would be indicated by H&E dyeing results. Moreover, FLS cell viability was inhibited by combination treatment in vitro ( P < 0.05), and expression of osteoclasia-related genes (RANKL and OPG) was modified ( P < 0.05). Combination therapy would relive the synovium hypertrophy through depressing cell viability and osteoclasia through decreasing RANKL and increasing OPG expression. Otherwise, combination was superior to monotherapy.
- Subjects
TREATMENT of arthritis; INFLAMMATION; BONE density; TRANCE protein; INTERLEUKIN-17; COLLAGEN; LABORATORY rats
- Publication
Rheumatology International, 2013, Vol 33, Issue 7, p1845
- ISSN
0172-8172
- Publication type
Article
- DOI
10.1007/s00296-013-2674-7