Research article
Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis
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* Corresponding author: Hassan Fahmi h.fahmi@umontreal.ca
1 Osteoarthritis Research Unit, Research Centre of the University of Montreal Hospital Center (CR-CHUM), Notre-Dame Hospital, Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada
2 Department of Medicine, University of Montreal, Montreal, Quebec H2L 4M1, Canada
3 Research Centre, Sacré-Coeur Hospital, Gouin Boulevard West, Montreal, Quebec H4J 1C5 Canada
4 Centre de Convalescence, de Charmilles Pavillion, des Laurentides Boulevard, Montreal, Quebec H7M 2Y3 Canada
Arthritis Research & Therapy 2009, 11:R44 doi:10.1186/ar2652
Published: 18 March 2009Abstract
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-1β-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-1β 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)γ was evaluated using transient transfection experiments and the PPARγ 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-1β-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 PPARγ, and GW9662 prevented their suppressive effect on MMP-1 and MMP-13 production, suggesting the involvement of PPARγ 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-1β-induced MMP-1 and MMP-13 expression in a PPARγ-dependent pathway. These data suggest that 15-lipoxygenases may have chondroprotective properties by reducing MMP-1 and MMP-13 expression.