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

Gendron, Christi, Kashiwagi, Masahide, Hughes, Clare Elizabeth ORCID: https://orcid.org/0000-0003-4726-5877, Caterson, Bruce ORCID: https://orcid.org/0000-0001-6016-0661 and Nagase, Hideaki 2003. TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors. FEBS Letters 555 (3) , pp. 431-436. 10.1016/S0014-5793(03)01295-X

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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-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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0014-5793
Last Modified:	27 Oct 2022 08:46
URI:	https://orca.cardiff.ac.uk/id/eprint/63376

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