Figure 2

HMGB1 blockade attenuates the histological severity of arthritis in DNase II^−/− × IFN-IR^-/- mice. Histopathology of joint specimens were evaluated, where signs of cell infiltration, cartilage destruction and bone erosions were determined and designated a score on a scale from 0 (normal appearance) to 3 (maximal pathology), as described in Materials and Methods. A significant lower score for all parameters was recorded in anti-HMGB1 mAb (2G7)-treated mice (n = 8) compared with control mice (n = 9). Representative micrographs illustrating articular joints stained with Safranin O after HMGB1 blocking therapy (B) and after control treatment with vehicle alone (C) are shown. Note destained cartilage layers (solid arrow) reflecting loss of matrix proteoglycans, massive cell infiltration and synovial hyperplasia invading into subchondral bone (dotted arrow) in control-treated articular tissue (C), compared with that of a 2G7-treated mouse, expressing more homogenous cartilage staining and preserved joint morphology (B). c, cartilage; js, joint space; s, synovial tissue. Original magnification 125×. **P < 0.01; ***P < 0.001. Differences in histopathology score between studied groups were analyzed by two-tailed, nonparametric Mann-Whitney test.