Hydrogen sulfide inhibits the calcification and osteoblastic differentiation of vascular smooth muscle cells

Kidney Int. 2011 Oct;80(7):731-9. doi: 10.1038/ki.2011.212. Epub 2011 Jun 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Cystathionine gamma-Lyase / metabolism
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Hydrogen Sulfide / metabolism
  • Hydrogen Sulfide / pharmacology*
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / pathology
  • Models, Biological
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Phosphates / metabolism
  • Vascular Calcification / etiology
  • Vascular Calcification / metabolism
  • Vascular Calcification / prevention & control*


  • Phosphates
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide