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

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 1 Ns generating peak forces in the range of 600 N using a 4 mm diameter indenter. Eight millimeter cartilage plugs containing the 4 mm diameter impacted core and a 4 mm adjacent ring were removed and cultured with or without P188 surfactant (8 mg/ml), caspase-3 (10 uM), or caspase-9 (2 uM) inhibitors for 48 h. 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<0.05) in the core and by about 30% in the ring in comparison with the impacted untreated control at all time points. P188 also prevented radial expansion of apoptosis in the ring region especially in the first 7 days post-impaction (7.5% Tunel-positive cells vs 46% in the untreated control; P<0.01). Inhibitors of caspase-3 or -9 were effective in reducing cell death in the impacted core only at early time points, but were ineffective in doing so in the ring. Mankin score was significantly improved in the P188 and caspase-3 treated groups. CONCLUSIONS Early intervention with the P188 and caspase-3 inhibitor may have therapeutic potential in the treatment of cartilage defects immediately after injury.