No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells

Mol Cell Endocrinol. 2012 Oct 15;362(1-2):149-56. doi: 10.1016/j.mce.2012.06.004. Epub 2012 Jun 12.

Abstract

The aim of this study was to examine the effects of the OPG-RANKL-TRAIL system on proliferation, regulation of calcification-associated genes and calcification of human vascular smooth muscle cells (HVSMCs). Small interfering (si)RNA-mediated knockdown of OPG was followed by treatment of HVSMCs with recombinant RANKL or TRAIL. Regulation of a calcification-associated gene set was assayed by pathway analysis of microarray results. The lack of OPG in HVSMCs or treatment with RANKL or TRAIL did not affect proliferation of HVSMCs. In addition, OPG, RANKL or TRAIL did not modify the regulation of a calcification-associated gene set. Finally, in the long term calcification assay, we found that cells isolated from seven different human donors showed a great variability in the response to RANKL and insulin. However, overall RANKL and/or insulin did not affect the development of calcification of HVSMCs. These studies indicate that OPG knockdown does not alter the calcification process in HVSMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation*
  • Cells, Cultured
  • Gene Knockdown Techniques
  • Humans
  • Insulin / physiology
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology*
  • Myocytes, Smooth Muscle / physiology
  • Oligonucleotide Array Sequence Analysis
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism*
  • RANK Ligand / physiology*
  • RNA Interference
  • TNF-Related Apoptosis-Inducing Ligand / physiology*
  • Transcriptome
  • Vascular Calcification / genetics*
  • Vascular Calcification / metabolism

Substances

  • Insulin
  • Osteoprotegerin
  • RANK Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF11B protein, human
  • TNFSF10 protein, human
  • TNFSF11 protein, human