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- Title
Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids.
- Authors
Cho, Hongsik; Walker, Andrew; Williams, Jeb; Hasty, Karen A.
- 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.
- Subjects
ANTI-inflammatory agents; STEROID drugs; CARTILAGE diseases; ANALYSIS of variance; ANIMAL experimentation; ANISOTROPY; CARTILAGE cells; CELL culture; CELL physiology; ENZYME-linked immunosorbent assay; FLUORIMETRY; METALLOPROTEINS; MICE; NONSTEROIDAL anti-inflammatory agents; OSTEOARTHRITIS; POLYMERASE chain reaction; RESEARCH funding; RNA; STEROIDS; T-test (Statistics); TUMOR necrosis factors; WESTERN immunoblotting; CYCLOOXYGENASE 2; TREATMENT effectiveness; DIAGNOSIS; THERAPEUTICS
- Publication
BioMed Research International, 2015, Vol 2015, p1
- ISSN
2314-6133
- Publication type
Article
- DOI
10.1155/2015/595273