We have previously reported that while the Basic Copper Sulphate(WSDTY) secretion is regulated by Nox4 activity, the regulation of ADAMTS5 secretion is not redox dependent in C-20/A4 chondrocytes. To assess the impact of GSCG and GS on the secretion pattern of these proteases, C-20/A4 chondrocytes were pre-incubated with 100 or 500 μg/ml of GSCG or of GS respectively for 96 h in complete DMEM medium. Medium was then replaced by serum free DMEM and cells were stimulated (24 h) or not with 2 ng/ml IL-1β in presence or not of GSCG or of GS. Results showed an important increase in both pro-MMP1 and ADAMTS5 secretion in the cell culture medium after chondrocyte stimulation by IL-1β.
Interestingly, under these conditions, GSCG at 500 μg/ml was able to reduce significantly IL-1β-induced pro-MMP1 secretion (50%) while GS had not any significant effects. On the other hand, both GS and GSCG neutralized IL-1β induced ADAMTS5 secretion. Based on these data, we can assume that impact of GSCG on MMP1 depends on Cu and/or GR while effects on ADAMTS5 are dependent on GS.
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