PDGF Induces Osteoprotegerin Expression in Vascular Smooth Muscle Cells by Multiple Signal Pathways

FEBS Lett. 2002 Jun 19;521(1-3):180-4. doi: 10.1016/s0014-5793(02)02872-7.

Abstract

Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. Recent reports suggest that OPG may function as a protector of arterial calcification and survival of endothelial cells. However, the role and expression of OPG in vascular wall is unclear. Here we report that OPG was highly expressed in vascular smooth muscle cells (VSMC) but not in endothelial cells. Platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, tumor necrosis factor alpha and interleukin-1beta upregulated OPG expression in VSMC. Moreover, inhibition of phosphatidylinositol 3-kinase/Akt or P38-signal pathway abrogated PDGF-induced OPG expression. Our results suggest that OPG may be an important determinant of vascular homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / pharmacology
  • Becaplermin
  • Carrier Proteins / genetics
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression*
  • Glycoproteins / genetics*
  • Humans
  • Interleukin-1 / pharmacology
  • Ligands
  • MAP Kinase Signaling System
  • Membrane Glycoproteins / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Osteoprotegerin
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-sis
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Tumor Necrosis Factor / genetics*
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Carrier Proteins
  • Glycoproteins
  • Interleukin-1
  • Ligands
  • Membrane Glycoproteins
  • Osteoprotegerin
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-sis
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Tumor Necrosis Factor-alpha
  • Fibroblast Growth Factor 2
  • Angiotensin II
  • Becaplermin
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases