Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes.
Both hyaluronic acid (HA) and cyclooxygenase-2 (COX-2) inhibitors are used in clinical practice in the treatment of osteoarthritis. There have been no reports regarding cross-talk between HA and COX-2 inhibitors in articular human chondrocytes. The purpose of this study was to investigate whether HA, COX-2 inhibitors or a combination of COX-2 inhibitors and HA have different effects in human articular between lower and highly degenerated chondrocytes. Isolated lower and highly degenerated chondrocytes were divided into 5 groups: ethanol (used as a control for the solvents), HA, COX-2 inhibitors, COX-2 inhibitors plus HA, or no additive. After incubating for 48 h, mitochondrial membrane potential analysis and western blotting of p38 and p44/42 mitogen-activated protein kinase (MAPK) were performed. Glycosaminoglycan, nitric oxide (NO) production and prostaglandin E2 (PGE2) concentrations were assessed. A combination of COX-2 inhibitors and HA resulted in dendritic, proliferating chondrocytes with strong red fluorescence enriched in the mitochondrial membrane, and indicated reduction of apoptosis in chondrocytes. COX-2 inhibitors alone, and a combination of COX-2 inhibitor and HA inhibited the activation of p38 in highly degenerated chondrocytes. A combination of COX-2 inhibitors and HA decreased NO production in highly degenerated chondrocytes. COX-2 inhibitors decreased PGE2 production, however, HA alone had no effect on PGE2 production. The present study demonstrated that COX-2 inhibitors and HA interacted synergistically the MAPK pathway and inhibition of NO production in highly degenerated chondrocytes. Administration of COX-2 inhibitors plus HA could be used as a new alternative way of treating osteoarthritis.
Takahashi
Toshiaki
T
Department of Orthopaedics, Kochi Medical School, Kochi University, Oko-cho, Nankoku, Kochi 783-8505, Japan. takahast@kochi-ms.ac.jp
Uemura
Yoshiki
Y
Taguchi
Hirokuni
H
Ogawa
Yasuhiro
Y
Yoshida
Shoji
S
Toda
Michio
M
Kobayashi
Toshihiro
T
Seguchi
Harumichi
H
Tani
Toshikazu
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002356:Cartilage / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007249:Inflammation; D020935:MAP Kinase Signaling System; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013997:Time Factors
D000276:Adjuvants, Immunologic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006025:Glycosaminoglycans; D008565:Membrane Proteins; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone