Vitamin A differentially regulates RANKL and OPG expression in human osteoblasts

Biochem Biophys Res Commun. 2004 Sep 10;322(1):162-7. doi: 10.1016/j.bbrc.2004.07.092.


All-trans-retinoic acid (ATRA) induces bone resorption, but the molecular mechanisms are unknown. We have studied the effect of ATRA on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) expression in human MG-63 osteosarcoma cells and primary osteoblast-like cultures. ATRA dose-dependently down-regulated protein levels of OPG in MG-63 cells, with a maximum (-56%) observed at a dose of 10(-6)M. This effect was confirmed with quantitative real-time PCR, where OPG mRNA was decreased after 4h (-68%) in primary cultures and after 8h (-87%) in MG-63 cells. The reduction in OPG expression was inhibited by a retinoic acid receptor (RAR)-antagonist and was mimicked by a RARbeta,gamma-agonist, indicating that the ATRA effect is mediated by these receptors. In primary cultures we found a threefold induction of RANKL mRNA expression. Thus, the RANKL/OPG ratio was markedly increased, suggesting a potential mechanism of ATRA-induced bone resorption.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Glycoproteins / metabolism*
  • Humans
  • Membrane Glycoproteins / metabolism*
  • NF-kappa B / metabolism*
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Osteoprotegerin
  • Osteosarcoma / metabolism*
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Retinoic Acid / metabolism*
  • Receptors, Tumor Necrosis Factor
  • Tretinoin / pharmacology*


  • Carrier Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • NF-kappa B
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Tretinoin