Tumor necrosis factor receptor 1 (TNFR1) silencing in the hepatic and splenic reticuloendothelial system ameliorates collagen-induced arthritis (CIA). One day after collagen booster, CIA-negative mice were injected intravenously with 3 × 108 ffu hairpin construct targeting TNFR1 (HpTNFR1) or hairpin non specific (HpNS). (a) Appearance of arthritis in fore and hind paws was monitored at indicated time points and scored for severity. (b) Histological analysis of inflammation ('infiltrate' and 'exudate') and proteoglycan depletion in patellar and femoral cartilage ('PG loss') from knee joints isolated at day 31. Data are represented as mean ± standard error of the mean (n = 6 mice), and statistical differences were calculated using Mann-Whitney U test. *P < 0.05, **P < 0.005. (c) Representative picture of safranin-O-stained tissue sections of knee joints from mice treated systemically with HpNS or HpTNFR1. Original magnification × 40. C, cartilage; F, femur; JS, joint space; P, patella; S, synovium.