[Articular cartilage in osteoarthritic patients: effects of diclofenac, celecoxib and glucosamine sulfate on inflammatory markers].
Osteoarthritis is a chronic and progressive joint disease. It is established by a complex process involving mechanical and biological alterations of the musculoskeletal system, which are generated by a great variety of interactions between genetic factors and extrinsic injuries. The pathogenesis of this disease is related to an increased and divergent production of inflammatory markers and proteolytic enzymes that promote the degradation and destruction of the extracellular matrix of articular and periarticular tissues. Cartilage samples were taken from 20 osteoarthritic patients during programmed surgical interventions. The cartilage samples were cultured in Dulbecco-Eagle medium, with or without the addition of NSAIDs or modulators of chondrocyte metabolism. The content of nitric oxide in the supernatant was quantified using the Griess reaction; the concentration of MMP-1 was quantified via double-sandwich ELISA. Untreated chondrocyte cultures produced 1950 +/- 665 ng/ml MMP-1. With the addition of Diclofenac this value decreased to 1140 +/- 155 ng/ml, although this difference was not statistically significant (p < 0.06). However, in the presence of Celecoxib the level significantly dropped to 760 +/- 75 ng/ml (p < 0.01). Although the addition ofglucosamine did not produce such a noticeable reduction in the level of MMP-1 (950 +/- 89 ng/ml), it was statistically significant (p < 0.05). On the contrary, none of the drugs (Diclofenac, Celecoxib, Glucosamine) modified the level of nitric oxide which had a mean value of 47.3 +/- 4.9 microM in the control samples. This investigation evidenced the inability of Diclofenac to significantly modify the production of proteolytic enzymes in osteoarthritic chondrocyte cultures. However, both Celecoxib and Glucosamine significantly reduced the production of MMP-1. On the contrary, none of the drugs used in this study managed to modify the concentration of nitric oxide. To the present day, no drugs have been found to be efficient in altering the natural course of the disease, requiring further investigation.
Brizuela
Nilda Y
NY
Departamento de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
Montrull
Hilda L
HL
Demurtas
Silvia L
SL
Meirovich
Carlos I
CI
D000368:Aged; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects*; D000068579:Celecoxib; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005944:Glucosamine / Q000494:pharmacology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases; D000068579:Celecoxib; D005944:Glucosamine