Selective COX-2 inhibition is favorable to human early and late-stage osteoarthritic cartilage: A human in vitro study

Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of osteoarthritis (OA). For the outcome of treatment the direct effects of NSAIDs on cartilage may be more important than indirect effects on inflammation, considered being secondary in OA. For clinical practice, it is relevant to study effects of NSAIDs on early stages of OA. Therefore we studied the direct effects of celecoxib on human degenerated OA cartilage and compared the effects with those on human healthy cartilage and human end-stage OA cartilage. Methods: Degenerated, late-stage OA, and healthy human articular cartilage were exposed (7 days of culture) to celecoxib (0.1-10 μM). Changes in cartilage proteoglycan turnover (synthesis, retention, and release), proteoglycan content, prostaglandin E₂ (PGE₂) and nitric oxide (NO) production were determined. Results: Both degenerated and established OA cartilage showed its characteristic changes in proteoglycan turnover (all P < 0.05). Celecoxib at 1 μM was able to increase synthesis of degenerated cartilage and normalize both releases of newly formed and resident proteoglycans. Importantly, 1 μM celecoxib influenced matrix integrity by enhancing proteoglycan content. Similar results were found for end-stage OA cartilage. Enhanced PGE₂ production in degenerative and OA cartilage could be decreased by celecoxib, whereas no effect on enhanced NO production was found. No significant effects of celecoxib on normal cartilage were found. Discussion: Celecoxib, in a clinical relevant concentration, showed in vitro a significant beneficial effect, not only on late-stage OA but also on more early stages of OA, whereas healthy cartilage remained unaffected, suggesting chondroprotective properties of celecoxib in the treatment of degenerative joint disorders.