title: Hydrogen sulfide inhibits the calcification and osteoblastic differentiation of vascular smooth muscle cells.
abstract: Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is involved in the pathogenesis of vascular calcification. Hydrogen sulfide (H(2)S) is a gas endogenously produced by cystathionine γ-lyase in VSMC. Here we determined whether H(2)S plays a role in phosphate-induced osteoblastic transformation and mineralization of VSMC. Hydrogen sulfide was found to inhibit calcium deposition in the extracellular matrix and to suppress the induction of the genes involved in osteoblastic transformation of VSMC: alkaline phosphatase, osteocalcin, and Cbfa1. Moreover, phosphate uptake and phosphate-triggered upregulation of the sodium-dependent phosphate cotransporter (Pit-1) were also prevented by H(2)S. Reduction of endogenous production of H(2)S by inhibition of cystathionine γ-lyase activity resulted in increased osteoblastic transformation and mineralization. Low plasma levels of H(2)S, associated with decreased cystathionine γ-lyase enzyme activity, were found in patients with chronic kidney disease receiving hemodialysis. Thus, H(2)S is a potent inhibitor of phosphate-induced calcification and osteoblastic differentiation of VSMC. This mechanism might contribute to accelerated vascular calcification in chronic kidney disease.
authors.affiliation: Hemostasis, Thrombosis and Vascular Biology Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Zavaczki
authors.forename: Viktória
authors.initials: V
authors.lastname: Jeney
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Zarjou
authors.forename: Melinda
authors.initials: M
authors.lastname: Oros
authors.forename: Mónika
authors.initials: M
authors.lastname: Katkó
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Varga
authors.forename: György
authors.initials: G
authors.lastname: Balla
authors.forename: József
authors.initials: J
authors.lastname: Balla
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D010710:Phosphates; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide