Objective: The aim of this study was to examine whether anti-inflammatory interleukin-10 ( IL-10) exerts chondroprotective effects in an in vitro model of a single mechanical injury of mature articular cartilage. Method: Articular cartilage was harvested from the femoro-patellar groove of adult cows ( Bos taurus) and cultured w/o bovine IL-10. After 24 h of equilibration explants were subjected to an axial unconfined compression ( 50% strain, velocity 2 mm/s, held for 10 s). After 96 h cell death was measured histomorphometrically ( nuclear blebbing, NB) and the release of glycosaminoglycans ( GAG, DMMB assay) and nitric oxide ( NO, Griess-reagent) were analyzed. mRNA levels of matrix degrading enzymes and nitric oxide synthetase were measured by quantitative real time PCR. Differences between groups were calculated using a one-way ANOVA with a Bonferroni post hoc test. Results: Injurious compression significantly increased the number of cells with NB, release of GAG and nitric oxide and expression of MMP-3, -13, ADAMTS-4 and NOS2. Administration of IL-10 significantly reduced the injury related cell death and release of GAG and NO, respectively. Expression of MMP-3, -13, ADAMTS-4 and NOS2 were significantly reduced. Conclusion: Joint injury is a complex process involving specific mechanical effects on cartilage as well as induction of an inflammatory environment. IL-10 prevented crucial mechanisms of chondrodegeneration induced by an injurious single compression. IL-10 might be a multipurpose drug candidate for the treatment of cartilage-related sports injuries or osteoarthritis (OA). (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.