Animals treated with oxaliplatin demonstrated reduced cell infiltration, cartilage and bone destruction as well as less cytosolic and extracellular HMGB1. Oxaliplatin treated mice (n = 8 with a mean clinical score of 1.0) and mice given vehicle alone (n = 8 with a mean clinical score of 4.8) (a) were killed on day 36 PI and intra-articular effects of oxaliplatin were evaluated by immunohistochemistry. Cell infiltration (b), cartilage (c) and bone (d) destruction were all significantly lower in oxaliplatin treated mice. Representative micrographs illustrating HMGB1 staining (in brown) in synovial tissue where an abundant cytosolic and extracellular HMGB1 staining was evident in mice treated with control vehicle (e) as compared to the low extranuclear HMGB1 expression in oxaliplatin treated mice (f). Sequential sections stained with Safranin O demonstrating reduced proteoglycan content in articular cartilage in the control (g) than in oxaliplatin treated animals (h). Signs of pronounced articular destructions are more evident in control treated animals, where destained cartilage layers reflected loss of matrix proteoglycans (see arrow). No cartilage destruction was detected in oxaliplatin treated mice indicated by a homogenous cartilage staining. CI, cell infiltration, JC, joint cavity, B, bone, C, cartilage. The boxes represent 25th to 75th percentiles and the lines inside the boxes stand for the median. The lines outside the boxes reflect 10th and 90th percentiles and circles indicate outliers. p = 0.05. Animals: control n = 8, oxaliplatin n = 8. Paws: control n = 32, oxaliplatin n = 32.