Glucosamine Inhibits IL-1beta-induced NFkappaB Activation in Human Osteoarthritic Chondrocytes

Osteoarthritis Cartilage. 2003 Apr;11(4):290-8. doi: 10.1016/s1063-4584(03)00028-1.

Abstract

Objective: Glucosamine sulfate (GS) is a commonly used drug for the treatment of osteoarthritis. The mechanism of the action of this drug does, however, remain to be elucidated. In human osteoarthritic chondrocytes (HOC) stimulated with a proinflammatory cytokine, we studied whether GS could modify the NFkappaB activity and the expression of COX-2, a NFkappaB-dependent gene.

Methods: Using HOC in culture stimulated with interleukin-1 beta (IL-1beta), the effects of GS on NFkappaB activation, nuclear translocation of NFkappaB/Rel family members, COX-1 and COX-2 expressions and syntheses and prostaglandin E2 (PGE2) concentration were studied.

Results: GS significantly inhibited NFkappaB activity in a dose-dependent manner, as well as the nuclear translocation of p50 and p65 proteins. Furthermore, GS-preincubated IL-1beta-stimulated HOC showed an increase in IkappaBalpha in the cell cytoplasm in comparison with HOC incubated with IL-1beta alone. GS also inhibited the gene expression and the protein synthesis of COX-2 induced by IL-1beta, while no effect on COX-1 synthesis was seen. GS also inhibited the release of PGE2 to conditioned media of HOC stimulated with IL-1beta.

Conclusions: GS inhibits the synthesis of proinflammatory mediators in HOC stimulated with IL-1beta through a NFkappaB-dependent mechanism. Our study further supports the role of GS as a symptom- and structure-modifying drug in the treatment of OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / pharmacology
  • Blotting, Western / methods
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis
  • Electrophoretic Mobility Shift Assay / methods
  • Fluorescent Antibody Technique / methods
  • Galactosamine / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Glucosamine / pharmacology*
  • Humans
  • Interleukin-1 / metabolism*
  • Isoenzymes / biosynthesis
  • Membrane Proteins
  • NF-kappa B / metabolism*
  • Osteoarthritis, Knee / metabolism*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis

Substances

  • Interleukin-1
  • Isoenzymes
  • Membrane Proteins
  • NF-kappa B
  • Galactosamine
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Glucosamine
  • Acetylglucosamine