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.
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.
authors: Department of Pharmacy, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhong Shan Road, Nanjing 210008, Jiang Su, China.
authors: Yao
authors: Y
authors: Yao
authors: Cong-zhu
authors: CZ
authors: Ding
authors: Yun
authors: Y
authors: Fang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024043:Collagen Type II; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D008727:Methotrexate / Q000494:pharmacology*; D053244:Osteoprotegerin / Q000097:blood / Q000378:metabolism; D053245:RANK Ligand / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; C515934:Il17a protein, rat; D020381:Interleukin-17; D007555:Isoxazoles; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C506032:Tnfrsf11b protein, rat; D000077339:Leflunomide; D008727:Methotrexate