TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors |
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Authors: | Gendron Christi Kashiwagi Masahide Hughes Clare Caterson Bruce Nagase Hideaki |
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Institution: | Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, W6 8LH, London, UK. |
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Abstract: | Aggrecanases are considered to play a key role in the destruction of articular cartilage during the progression of arthritis. Here we report that the N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3 (N-TIMP-3), but not TIMP-1 or TIMP-2, inhibits glycosaminoglycan release from bovine nasal and porcine articular cartilage explants stimulated with interleukin-1alpha or retinoic acid in a dose-dependent manner. This inhibition is due to the blocking of aggrecanase activity induced by the catabolic factors. Little apoptosis of primary porcine chondrocytes is observed at an effective concentration of N-TIMP-3. These results suggest that TIMP-3 may be a candidate agent for use against cartilage degradation. |
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Keywords: | Interleukin-1 Retinoic acid ADAMTS Proteoglycan Arthritis |
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