Hyaluronic acid abrogates nitric oxide-dependent stimulation of collagen degradation in cultured human chondrocytes.
Experimental inflammation induced in cultured chondrocytes by inflammatory cytokine IL-1 beta stimulates collagen degradation by metalloproteinases. We propose that nitric oxide (NO) may represent down stream signaling molecule of IL-1-induced collagen degradation in chondrocytes. It was found that IL-1 beta induced the activity of MMP-2 and MMP-9 during the 48 h time course of the experiment, especially after 24h incubation, while DETA/NO, donor of NO, stimulated the process at 12h incubation. The mechanism of IL-1-dependent stimulation of NO production was found at the level of iNOS expression and activation of NF-kappaB. We found that hyaluronic acid (HA) counteracted IL-induced degradation of collagen in chondrocytes. Although, HA by itself had no effect on the metaloproteinases activity, when added to IL-1 beta or DETA/NO treated chondrocytes it contributed to the restoration of the MMPs activity to the control level. The mechanism of this phenomenon involves inhibition of NF-kappaB activation. The data suggest that NO may represent a target molecule for protective effect of hyaluronic acid on interleukin-1-induced stimulation of metaloproteinases activity in cultured human chondrocytes.
Department of Medicinal Chemistry, Medical University in Białystok, Kilińskiego 1, 15-089 Bialystok, Poland.
Arkadiusz
A
Surazynski
Wojciech
W
Miltyk
Robert
R
Czarnomysy
Joanna
J
Grabowska
Jerzy
J
Palka
D015153:Blotting, Western; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D047468:Immunoprecipitation; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000276:immunology / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*
D053583:Interleukin-1beta; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9