Single Impact Cartilage Trauma And Tnf-Alpha: Interactive Effects Do Not Increase Early Cell Death And Indicate The Need For Bi-/Multidirectional Therapeutic Approaches

Blunt trauma of articular cartilage, often resulting from accidents or sports injuries, is associated with local inflammatory reactions and represents a major risk factor for development of post-traumatic osteoarthritis. TNF-alpha is increased in synovial fluid early after trauma, potentiates injury-induced proteoglycan degradation and may act proapoptotic under permissive conditions. We asked whether TNF-alpha also influences chondrocyte death, gene expression of catabolic and anabolic markers and the release of proinflammatory mediators in the early post-traumatic phase. Interactive effects of a defined single impact trauma (0.59 J) and TNF-alpha (100 ng/ml) on human early-stage osteoarthritic cartilage were investigated in vitro over 24 h. Exposure of traumatized cartilage to TNF-alpha did not increase chondrocyte death. IL-6-synthesis was augmented by trauma, TNF-alpha and combined treatment. The impact increased the release of PGE2 and PGD2 in the presence and absence of TNF-alpha to a similar extent while TNF-alpha alone showed no effect. In contrast, NOS2A-expression and nitric oxide (NO)-release were not affected by trauma but significantly increased by TNF-alpha. Expression of OPG and RANKL was not affected by TNF-alpha but modulated by trauma. TNF-alpha with and without trauma significantly induced MMPI gene expression. These results indicate that TNF-alpha does not potentiate early cell death in early-stage osteoarthritic cartilage after blunt injury. However, trauma and TNF-alpha z showed independent and interactive effects concerning prostaglandin and NO release. TNF-alpha probably contributes to cartilage degradation after trauma by an early induction of MM PI gene expression. Our study confirms that an anti-TNF-alpha therapy may have inhibitory effects on catabolic and, partly, on inflammatory processes after a single impact trauma. As TNF-alpha does not contribute to the loss of chondrocytes in the initial post-traumatic phase, a combination with pharmaco-therapeutic strategies reducing early cell death could be reasonable.