Role of GSH/GSSG redox couple in osteogenic activity and osteoclastogenic markers of human osteoblast-like SaOS-2 cells

摘要

This study comprised a comprehensive analysis of the glutathione (GSH) redox system during osteogenic differentiation in human ostcoblast-likc SaOS-2 cells. For the first time, a clear relationship between expression of specific factors involved in bone remodeling and the changes in the GSH/ oxidized GSH (GSSG) redox couple induced during the early phases of the differentiation and mineralization process is shown. The findings show that the time course of differentiation is characterized by a decrease in the GSH/GSSG ratio, and this behavior is also related to the expression of osteoclastogenic markers. Maintenance of a high GSH/GSSG ratio due to GSH exposure in the early phase of this process increases mRNA levels of osteogenic differentiation markers and mineralization. Conversely, these events arc decreased by a low GSH/GSSG ratio in a reversible manner. Redox regulation of runt-related transcription factor-2 (RUNX-2) activation through phosphorylation is shown. An inverse relationship between RUNX-2 activation and extracellular signal-regulated kinases related to GSH redox potential is observed. The GSH/GSSG redox couple also affects ostcoclastogcncsis, mainly through ostcoprotegcrin down-regulation with an increase in the ratio of receptor activator of NF-kappa B Hgand to ostcoprotegcrin and vice versa. No redox regulation of receptor activator of NF-kapp B Hgand expression was found. These results indicate that the GSH/GSSG redox couple may have a pivotal role in bone remodeling and bone rcdox-dysrcgulatcd diseases. They suggest therapeutic use of compounds that arc able to modulate not just the GSH level but the intracellular redox system through the GSH/GSSG redox couple.