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Arthritis Res Ther. 2009;11(2):R44. doi: 10.1186/ar2652. Epub 2009 Mar 18.

Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis.

Author information

1
Osteoarthritis Research Unit, Research Centre of the University of Montreal Hospital Center, Notre-Dame Hospital, Montreal, Quebec, Canada. nadir.chabane@umontreal.ca

Abstract

INTRODUCTION:

15-Lipoxygenases and their metabolites have been shown to exhibit anti-inflammatory and immunomodulatory properties, but little is known regarding their expression and function in chondrocytes. The objective of this study was to evaluate the expression of 15-lipoxygenase-1 and -2 in human articular chondrocytes, and to investigate the effects of their metabolites 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids on IL-1beta-induced matrix metalloproteinase (MMP)-1 and MMP-13 expression.

METHODS:

The expression levels of 15-lipoxygenase-1 and -2 were analyzed by reverse transcription PCR and Western blotting in chondrocytes, and by immunohistochemistry in cartilage. Chondrocytes or cartilage explants were stimulated with IL-1beta in the absence or presence of 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids, and the levels of MMP-1 and MMP-13 protein production and type II collagen cleavage were evaluated using immunoassays. The role of peroxisome proliferator-activated receptor (PPAR)gamma was evaluated using transient transfection experiments and the PPARgamma antagonist GW9662.

RESULTS:

Articular chondrocytes express 15-lipoxygenase-1 and -2 at the mRNA and protein levels. 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids dose dependently decreased IL-1beta-induced MMP-1 and MMP-13 protein and mRNA expression as well as type II collagen cleavage. The effect on MMP-1 and MMP-13 expression does not require de novo protein synthesis. 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids activated endogenous PPARgamma, and GW9662 prevented their suppressive effect on MMP-1 and MMP-13 production, suggesting the involvement of PPARgamma in these effects.

CONCLUSIONS:

This study is the first to demonstrate the expression of 15-lipoxygenase-1 and -2 in articular chondrocytes. Their respective metabolites, namely 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids, suppressed IL-1beta-induced MMP-1 and MMP-13 expression in a PPARgamma-dependent pathway. These data suggest that 15-lipoxygenases may have chondroprotective properties by reducing MMP-1 and MMP-13 expression.

PMID:
19296842
PMCID:
PMC2688191
DOI:
10.1186/ar2652
[Indexed for MEDLINE]
Free PMC Article

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