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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.

Type

Journal article

Journal

FEBS Lett

Publication Date

18/12/2003

Volume

555

Pages

431 - 436

Keywords

Aggrecans, Animals, Apoptosis, Cartilage, Articular, Cattle, Cell Line, Chondrocytes, Culture Techniques, Endopeptidases, Extracellular Matrix Proteins, Glycosaminoglycans, Humans, Interleukin-1, Lectins, C-Type, Protease Inhibitors, Protein Structure, Tertiary, Proteoglycans, Recombinant Proteins, Swine, Tissue Inhibitor of Metalloproteinase-3, Tretinoin