Effects of Nonsteroidal Anti-inflammatory Drugs on Chondrogenic Differentiation

BACKROUND: NSAIDs represent a large class of drugs used for their analgesic and anti-inflammatory effects. Background Nevertheless, their effects on chondrogenic differentiation are not known. The present study examines the potential effects of five different NSAIDs, namely Etodolac, Dexketoprofen, Acetaminophen (Paracetamol), Lornoxicam and Ibuprofen on cell viability as well as chondrogenic differentiation using a mouse embryonic ATDC5-cell-derived chondrocyte model. METHODS: ATDC5 cells were treated with different concentrations of the NSAIDs. The viablility was evaluated by MTT assay while q-PCR analyses of gene expression of chondrogenic markers (Aggrecan, SOX-9, COL1 and COL2) on 5th & 10th day. Early glycosaminoglycan changes in articular cartilage were determined by safranin-O staining. RESULTS: No clinical relevant concentration of Lornoxicam, Dexketoprofen and Ibuprofen proved beneficial influence on cell survival. Dexketoprofen and Lornoxicam promoted chondrogenesis through a significant increase of the Aggrecan and COL2 gene expression(levels) when compared to control samples. Histological staining further revealed that Lornoxicam and Dexketoprofen significantly increased glycosaminoglycan content, suggestive of enhanced chondrogenic differentiation. CONCLUSION: Of all investigated NSAIDs, lornoxicam performed best in terms of chondrogenic differentiation and appears as the most suited for therapeutic approaches targeting cartilage repair / regeneration. These results are further improved with ITS supplementation, indicating a potential synergistic effect to improve cartilage tissue engineering. Keywords: NSAIDs, chondrogenic differentiation, Lornoxicam and Dexketoprofen