Objectives: Recent studies showed beneficial effects of COX-2 inhibition on proteoglycan turnover of both IL-1β/tumour necrosis factor α (TNFα) damaged cartilage and of osteoarthritic cartilage. Although proteoglycan release and content were normalised, proteoglycan synthesis was only partially influenced. Prostaglandin-E2 is the main product formed by COX-2. We therefore evaluate the role of prostaglandin-E2 in relation to nitric oxide in disturbing cartilage proteoglycan turnover.
Methods: Human healthy cartilage, alone or in the presence of IL-1β+TNFα, was cultured for 7 days with or without prostaglandin-E2 or the selective COX-2 inhibitor (celecoxib 10 μM). Changes in cartilage matrix proteoglycan turnover, levels of prostaglandin-E2 and nitric oxide were determined.
Results: Proteoglycan synthesis and release of the cartilage were not affected by prostaglandin-E2 alone. Addition of IL-1β+TNFα to healthy cartilage resulted in inhibition of proteoglycan synthesis and increase in proteoglycan release. When prostaglandin-E2 was added, in addition to IL-1β+TNFα, proteoglycan release increased further, but proteoglycan synthesis was not influenced further. Addition of a selective COX-2 inhibitor to the IL-1β+TNFα treated cartilage inhibited the enhanced prostaglandin-E2 production and almost completely normalised proteoglycan release, whereas synthesis remained unaffected. Also, the enhanced NO-levels remained elevated. Prostaglandin-E2 levels correlated significantly with proteoglycan release, whereas NO levels correlated significantly with proteoglycan synthesis.
Conclusion: The present results suggest involvement of prostaglandin-E2 in enhanced cartilage proteoglycan release but not synthesis, although healthy cartilage has to be sensitised by IL-1β+tumour necrosis factor α (TNFα). IL-1β+TNFα induced NO seems to be involved in inhibition of proteoglycan synthesis, independent of prostaglandin-E2, and thus seems insensitive to regulation by (selective) COX-2 inhibitors.
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Competing interests: None.
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