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Human articular chondrocytes express 15-lipoxygenase-1 and -2: Potential role in osteoarthritis
Arthritis Research & Therapy, 03/24/09

Chabane N et al. - Study reports the expression of 15-lipoxygenase-1 and -2 in articular chondrocytes; their metabolites suppressed IL-1β -induced MMP1 and 13 expression in a PPAR-γ dependent pathway, suggesting that 15-lipoxygenases may have chondroprotective properties by reducing MMP-1 and -13 expression.

Methods

Study to evaluate the expression of 15-lipoxygenase-1 and -2 in human articular chondrocytes
Eeffects of their metabolites, 13(S)-hydroxy octadecadienoic acid and 15(S)-hydroxyeicosatetraenoic, on IL-1β-induced MMP-1 and -13 expression was also investigated
Expression was analyzed by RT-PCR and WB in chondrocytes, and by IHC in cartilage
Chondrocytes or cartilage explants were stimulated with IL-1β in the absence or presence of 13(S)-hydroxy octadecadienoic acid and 15(S)-hydroxyeicosatetraenoic
Level of MMP-1 and -13 protein production and type II collagen cleavage evaluated by immunoassays
Role of PPAR-γ evaluated using transient transfection experiments and the PPAR-γ antagonist GW9662

Results

Articular chondrocytes express 15-lipoxygenase-1 and -2 at the mRNA and protein levels
13(S)-hydroxy octadecadienoic acid and 15(S)-hydroxyeicosatetraenoic dose-dependently decreased IL-1β-induced MMP-1 and -13 protein and mRNA expression, and type II collagen cleavage
Effect on MMP-1 and -13 expression did not require de novo protein synthesis
13(S)-hydroxy octadecadienoic acid and 15(S)-hydroxyeicosatetraenoic activated endogenous PPAR-γ and GW9662 prevented their suppressive effect on MMP-1 and -13 production

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