Single impact trauma in human early-stage osteoarthritic cartilage: Implication of prostaglandin D2 but no additive effect of IL-1β on cell survival

Injury to articular cartilage is often associated with an inflammatory reaction and frequently results in the development of post-traumatic osteoarthritis (post-traumatic OA). Cell death, inflammation and loss of proteoglycans participate in these mechanisms with p38MAPK being one of the pivotal signaling kinases. Therefore, the interaction of trauma and of the pro-inflammatory cytokine IL-1 beta was investigated in an in vitro tissue model of human osteoarthritic cartilage. Trauma was induced by impacting cartilage explants with a drop-tower system and its effect was measured in terms of cell survival, gene expression and the release of mediators. In addition, the effect of concomitant IL-1 beta stimulation and p38MAPK inhibition by SB203580 was investigated. We found a significant decrease in chondrocyte viability after trauma, but no additional effect of IL-1 beta stimulation. SB203580 had a tendency to improve cell survival suggesting a role for p38 signaling in cell viability after impact in an inflammatory environment. We showed that various mediators are released in response to trauma with or without IL-1 beta stimulation, differing in composition and time response. Trauma resulted in an increased release of IL-6, whereas TNF-alpha and IL-1 beta release was unaffected. Prostaglandin (PG) and NO synthesis pathways were both affected by trauma and/or IL-1 beta. We demonstrate for the first time an elevated release of prostaglandin D2 (PGD2) by human articular cartilage in response to a single mechanical impact. The up-regulation of mediators was time-dependent, with a more early increase of PGD2 compared to prostaglandin E2 (PGE2) and a late induction of NO by co-stimulation with IL-1 beta between 6 and 24 h.