Research Papers:

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

Elisabetta Lambertini, Letizia Penolazzi, Marco Angelozzi, Francesco Grassi, Laura Gambari, Gina Lisignoli, Pasquale de Bonis, Michele Cavallo and Roberta Piva _

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Oncotarget. 2017; 8:101686-101696. https://doi.org/10.18632/oncotarget.21514

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Elisabetta Lambertini1, Letizia Penolazzi1, Marco Angelozzi1, Francesco Grassi2, Laura Gambari2, Gina Lisignoli3, Pasquale De Bonis4, Michele Cavallo4 and Roberta Piva1

1Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy

2Ramses Laboratory, Rizzoli Orthopedic Institute, Bologna, Italy

3Laboratory of Immunorheumatology and Tissue Regeneration, Rizzoli Orthopedic Institute, Bologna, Italy

4Department of Neurosurgery, S. Anna University Hospital, Ferrara, Italy

Correspondence to:

Roberta Piva, email: [email protected]

Keywords: cystathionine gamma-lyase; H2S; osteoblasts; bone; estrogen receptor alpha

Received: July 12, 2017     Accepted: September 04, 2017     Published: October 04, 2017


Hydrogen sulfide (H2S), generated in the osteoblasts predominantly via cystathionine-γ-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 (ERα) 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 ERα overexpression. Bioinformatic analysis, luciferase reporter assay and ChIP assay were performed to investigate ERα 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 ERα – mediated positive regulation of CSE expression. All osteoblast samples responded to ERα over-expression increasing the levels of CSE protein in a comparable manner. Notably, the ERα 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.

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