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TIMP‐3 inhibits aggrecanase‐mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors
Author(s) -
Gendron Christi,
Kashiwagi Masahide,
Hughes Clare,
Caterson Bruce,
Nagase Hideaki
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01295-x
Subject(s) - aggrecanase , cartilage , chemistry , glycosaminoglycan , matrix metalloproteinase , catabolism , microbiology and biotechnology , aggrecan , explant culture , osteoarthritis , metalloproteinase , biochemistry , in vitro , articular cartilage , anatomy , biology , medicine , pathology , enzyme , alternative medicine
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‐1α 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.