Vitamin A differentially regulates RANKL and OPG expression in human osteoblasts.

Abstract

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.

• Authors: A Jacobson, S Johansson, M Branting, H Melhus
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 322 Issue 1 Pg. 162-7 (Sep 10 2004) ISSN: 0006-291X [Print] United States
• PMID: 15313187 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, 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)