Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

• Published in: BioMed research international 2015-01, Vol.2015 (2015), p.1-10
• Main Authors: Hasty, Karen A., Williams, Jeb, Walker, Andrew, Cho, Hongsik
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Cartilage - drug effects; Cartilage - pathology; Cell Survival - drug effects; Chondrocytes - drug effects; Chondrocytes - pathology; COX-2 inhibitors; Cyclooxygenase 2 Inhibitors - therapeutic use; Disease Models, Animal; Dosage and administration; Drug therapy; Fluorescent Dyes - metabolism; Free radicals; Gene Expression Regulation - drug effects; Humans; Infrared imaging systems; Knee Joint - pathology; Male; Matrix Metalloproteinase 1 - metabolism; Medical research; Mice, Inbred C57BL; Nitric oxide; Nonsteroidal anti-inflammatory drugs; Osteoarthritis; Osteoarthritis - drug therapy; Osteoarthritis - pathology; Pain; Rodents; Steroids; Steroids - pharmacology; Steroids - therapeutic use; Studies; Surgery; Sus scrofa; Tumor Necrosis Factor-alpha - pharmacology; Veterans
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2015/595273

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA) mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.