Selective COX-2 inhibitor regulates the MAP kinase signaling pathway in human osteoarthritic chondrocytes after induction of nitric oxide.
The purpose of this study was to examine the effect of cyclooxygenase-2 (COX-2) inhibitors on the mitogen-activated protein (MAP) kinase signaling pathway and synthesis of glucosaminoglycan after nitric oxide (NO) induction in articular human chondrocytes. After NO induction, the cells were divided into three groups that were treated with either ethanol (control); a selective COX-2 inhibitor (Celecoxib), or no additive, and evaluated. There were no differences in the effect of the selective COX-2 inhibitor on mitochondrial membrane potential or Annexin V levels. However, Celecoxib significantly decreased prostaglandin E2 (PGE2) production. Celecoxib also decreased the phosphorylation state of p38 and p44/42 of MAP kinase. The ratio of chondroitin-6 sulfate (C6S)/C4S was increased in response to the exposure to Celecoxib. Celecoxib did not affect apoptosis, but decreased the activation of MAP kinase in osteoarthritic chondrocytes after NO induction. NO-induced OA chondrocytes were associated with the p38 and the p44/42 MAPK signaling pathways, in a pathway that is distinct from PGE2-mediated apoptosis.
Takahashi
Toshiaki
T
Department of Orthopaedic Surgery, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. takahast@m.ehime-u.ac.jp
Ogawa
Yasuhiro
Y
Kitaoka
Kenichi
K
Tani
Toshikazu
T
Uemura
Yoshiki
Y
Taguchi
Hirokuni
H
Kobayashi
Toshihiro
T
Seguchi
Harumichi
H
Yamamoto
Haruyasu
H
Yoshida
Shoji
S
D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002356:Cartilage / Q000378:metabolism; D000068579:Celecoxib; D002469:Cell Separation; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D008564:Membrane Potentials; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D017304:Annexin A5; D017077:Culture Media, Conditioned; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006025:Glycosaminoglycans; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D049452:Green Fluorescent Proteins; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D000068579:Celecoxib; D015232:Dinoprostone