TIMP‐3 inhibits aggrecanase‐mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors

FEBS Letters

Hughes, Clare¹  Gendron, Christi²  Caterson, Bruce¹  Kashiwagi, Masahide²  Nagase, Hideaki² 

[1] Connective Tissue Laboratories, Cardiff School of Biosciences, University of Cardiff, Cardiff CF10 3US, UK;Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, London W6 8LH, UK

关键词: Interleukin-1;    Retinoic acid;    ADAMTS;    Proteoglycan;    Arthritis;    ADAMTS;    a metalloproteinase with disintegrin and thrombospondin type-1 motifs;    AP;    alkaline phosphatase;    DMEM;    Dulbecco's modified Eagle's medium;    DMMB;    dimethylmethylene blue;    GAG;    glycosaminoglycan;    IL-1α;    interleukin-1α;    MMP;    matrix metalloproteinase;    N-TIMP;    N-terminal inhibitory domain of tissue inhibitor of metalloproteinases;    PBS;    phosphate-buffered saline;    SNP;    sodium nitroprusside;    TIMP;    tissue inhibitor of metalloproteinases;   

DOI  :  10.1016/S0014-5793(03)01295-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown