Hydrogen sulfide down-regulates the expression and release of osteoprotegerin (OPG) by vascular endothelial cells

Excerpt

Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor (TNF) receptor family, initially characterized for its ability to inhibit the receptor activator of NF-kB ligand (RANKL)-stimulated formation of osteoclasts [1]. OPG also interacts with TNF-related apoptosis inducing ligand (TRAIL) [2], a different member of the TNF super-family whose extracellular domain shares a 35% homology with RANKL [3]. Several studies have demonstrated that OPG is elevated in the serum/plasma of patients affected by different types of cancer (reviewed in [4]), but the potential role of OPG with respect to cancer development/progression is unknown. Among different potential cellular sources of circulating OPG, endothelial cells represent a major source of OPG under basal conditions as well as in response to inflammatory stimuli [5]. Hydrogen sulfide (H₂S)—known for decades as a toxic gas—is endogenously generated from cysteine, in reactions catalyzed by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) [6‐8]. Mounting data on endogenously generated H₂S have now included this gas in the family of gasotransmitters, together with nitric oxide (NO) and carbon monoxide (CO), and its effects are intensively investigated both at the cellular and molecular level [7]. On these bases, the aim of the present study was to investigate in vitro the effect of H₂S on the expression and release of OPG by human vascular endothelial cells in the absence or presence of the pro-inflammatory cytokine TNF-α. …