Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes.

Abstract

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.

• Authors: Toshiaki Takahashi, Yoshiki Uemura, Hirokuni Taguchi, Yasuhiro Ogawa, Shoji Yoshida, Michio Toda, Toshihiro Kobayashi, Harumichi Seguchi, Toshikazu Tani
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 14 Issue 2 Pg. 139-44 (Aug 2004) ISSN: 1107-3756 [Print] Greece
• PMID: 15254755 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Glycosaminoglycans
• Membrane Proteins
• Nitric Oxide
• Hyaluronic Acid
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• Adjuvants, Immunologic (pharmacology)
• Apoptosis
• Blotting, Western
• Cartilage (metabolism)
• Chondrocytes (drug effects, metabolism)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprostone (metabolism)
• Drug Synergism
• Glycosaminoglycans (metabolism)
• Humans
• Hyaluronic Acid (pharmacology)
• Inflammation
• MAP Kinase Signaling System
• Membrane Potentials (drug effects)
• Membrane Proteins
• Mitochondria (metabolism)
• Nitric Oxide (metabolism)
• Osteoarthritis (drug therapy, enzymology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Time Factors