The expression of cystathionine gamma-lyase is regulated by estrogen receptor alpha in human osteoblasts

Hydrogen sulfide (H2S), generated in the osteoblasts predominantly via cystathionine-gamma-lyase (CSE), is bone protective. Previous studies suggested that the onset of bone loss due to estrogen deficiency is associated to decreased levels of H2S and blunted gene expression of CSE. However, there are still a lot of unknowns on how H2S levels influence bone cells function. The present study aims to explore the mechanisms by which estrogen may regulate CSE expression, in particular the role of estrogen receptor alpha (ER alpha) in human osteoblasts (hOBs). Vertebral lamina derived hOBs were characterized and then assessed for CSE expression by western blot analysis in the presence or absence of ER alpha overexpression. Bioinformatic analysis, luciferase reporter assay and ChIP assay were performed to investigate ER alpha recruitment and activity on hCSE gene promoter. Three putative half Estrogen Responsive Elements (EREs) were identified in the hCSE core promoter and were found to participate in the ER alpha - mediated positive regulation of CSE expression. All osteoblast samples responded to ER alpha over-expression increasing the levels of CSE protein in a comparable manner. Notably, the ER alpha recruitment on the regulatory regions of the CSE promoter occurred predominantly in female hOBs than in male hOBs. The obtained results suggest that CSE/H2S system is in relation with estrogen signaling in bone in a gender specific manner.