Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes.
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.
Largo
R
R
Inflammation Research Unit, Fundación Jiménez Díaz, Autonoma University, Madrid, Spain.
Alvarez-Soria
M A
MA
Díez-Ortego
I
I
Calvo
E
E
Sánchez-Pernaute
O
O
Egido
J
J
Herrero-Beaumont
G
G
D000117:Acetylglucosamine / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D005688:Galactosamine / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D005688:Galactosamine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D005944:Glucosamine; D000117:Acetylglucosamine