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TIMP-3 K26A/K45A and K42A/K110A protect cartilage for longer than the wild-type inhibitor. Porcine articular cartilage explants were cultured in cartilage medium with 0.1% FCS (250 μl) and/or wild-type TIMP-3, K26A/K45A, or K42A/K110A (100 nm). After 0, 1, 2, or 3 days, explants were stimulated with IL-1 (10 ng/ml) for 24 h, and aggrecan degradation was analyzed by a DMMB assay (mean ± S.D. (error bars), n = 3 biological replicates). *, p ≤ 0.05; **, p ≤ 0.01; ***, p ≤ 0.001.
