title: Study of osteoarthritis treatment with anti-inflammatory drugs: cyclooxygenase-2 inhibitor and steroids.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center and Campbell Clinic, Memphis, TN, USA ; Veterans Affairs Medical Center, Memphis, TN, USA.
authors.forename: Hongsik
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center and Campbell Clinic, Memphis, TN, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Walker
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center and Campbell Clinic, Memphis, TN, USA.
authors.forename: Jeb
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center and Campbell Clinic, Memphis, TN, USA ; Veterans Affairs Medical Center, Memphis, TN, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Hasty
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007719:Knee Joint / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use*; D034421:Sus scrofa; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D005456:Fluorescent Dyes; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1