Inducible hydrogen sulfide synthesis in chondrocytes and mesenchymal progenitor cells: is H2S a novel cytoprotective mediator in the inflamed joint?
Bottom Line: Oxidative stress-induced cell death was significantly inhibited by GYY4137 treatment but increased by pharmacological inhibition of H(2)S synthesis or by CBS/CSE-siRNA treatment.These data suggest CSE is an inducible source of H(2)S in cultured HACs and MPCs.H(2)S may represent a novel endogenous mechanism of cytoprotection in the inflamed joint, suggesting a potential opportunity for therapeutic intervention.
Affiliation: Peninsula Medical School, University of Exeter, St. Luke's Campus, Exeter, Devon, UK.Show MeSH
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Mentions: Figure 1A–C shows that under basal conditions chondrogenically differentiated MPCs expressed CBS and had detectable CSE. Densitometric analysis of CSE and CBS expression is shown in Figure 1D–E, respectively. Basal levels of H2S synthesis were significantly inhibited by AOAA (a CBS inhibitor) (Fig. 1F). In contrast, a small statistically insignificant decrease in H2S synthesis was observed after treatment with the CSE inhibitor PAG, suggesting that CBS was the predominant source of H2S under basal conditions. In contrast, treatment of MPCs with the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 significantly increased expression (Fig. 1A–E) and activity (Fig. 1F) of CSE but not CBS. Incubation of chondrocytes in alginate culture with TNF-α, IL-1β and IL-6 under the same experimental conditions as MPCs also resulted in significant increases in expression (Fig. 2A and B) and activity (Fig. 2C) of CSE but not CBS. In MPCs and chondrocytes PAG, but not AOAA, significantly inhibited cytokine-induced CSE activity, suggesting that CSE is an inducible source of H2S in these cells.
Affiliation: Peninsula Medical School, University of Exeter, St. Luke's Campus, Exeter, Devon, UK.