Knorpeltrauma und post-traumatische Inflammationsreaktion

Abstract

A trauma of articular cartilage is often associated with an inflammatory reaction and results in many cases in the development of post-traumatic osteoarthritis. The pathogenetic connection between inflammatory processes and cartilage degeneration is not clear so far. One of the pivotal signaling kinases in these degrading mechanisms is the p38 MAPK. In order to investigate the post-traumatic reactions, an in vitro model was developed. Human cartilage explants were mechanically impacted by using a drop-tower. Additionally to the mechanical stress a group was either stimulated with IL-1ß (IL) or C5a. Another group was stimulated with IL and the p38 MAPK-inhibitor SB203580. The post-traumatic effects were measured in terms of cell survival, gene expression and the release of mediators. A human in vitro co-culture system of cartilage explants with synovial fibroblasts (SF) was established to elucidate the role of the synovial tissue regarding inflammatory and catabolic reactions post trauma. A significant decrease in chondrocyte viability after trauma, but no additional effect of IL was detected. For the first time an elevated release of PGD2 by human articular cartilage in response to a single mechanical impact was demonstrated. Various other mediators (e.g. PGE2, NO, IL-6) were released in response to trauma ± IL stimulation. ACAN and COL2A1 gene expression was reduced after trauma + IL stimulation whereas MMP-1, -3, and -13 gene expression was elevated. Stimulation with C5a showed no effects concerning post-traumatic inflammatory and catabolic reactions. SB203580 had a tendency to improve cell survival and to reduce the release of proinflammatory mediators as well as the mRNA expression level of matrix-catabolic genes after impact in an inflammatory environment. Co-cultivation of cartilage explants with SF resulted in mutual effects post trauma including a decreased amount of viable chondrocytes and an increased release of prostaglandins and IL-6 after trauma.