Anti-apoptotic treatments prevent cartilage degradation after acute trauma to human ankle cartilage.

Summary Objectives To investigate the effect of anti-apoptotic agents on cartilage degradation after a single impact to ankle cartilage. Design Ten human normal tali were impacted with the impulse of 1Ns generating peak forces in the range of 600N using a 4mm diameter indenter. Eight millimeter cartilage plugs containing the 4mm diameter impacted core and a 4mm adjacent ring were removed and cultured with or without P188 surfactant (8mg/ml), caspase-3 (10uM), or caspase-9 (2uM) inhibitors for 48h. Results were assessed in the superficial and middle-deep layers immediately after injury at day 0 and at 2, 7 and 14 days after injury by live/dead cell and Tunel assays and by histology with Safranin O/fast green staining. Results A single impact to human articular cartilage ex vivo resulted in cell death, cartilage degeneration, and radial progression of apoptosis to the areas immediately adjacent to the impact. The P188 was more effective in preventing cell death than the inhibitors of caspases. It reduced cell death by more than 2-fold ( P P Conclusions Early intervention with the P188 and caspase-3 inhibitor may have therapeutic potential in the treatment of cartilage defects immediately after injury.