Vitamin A differentiall regulates RANKL and OPG expression in human osteoblasts
2004 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 322, no 1, 162-167 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2004. Vol. 322, no 1, 162-167 p.
Vitamin A, Osteoprotegerin, Bone resorption, Retinoic acid, Osteoporosis, Receptor for activation of NF-κB ligand, Retinoic acid receptor, RAR-antagonist, Osteoblast, Bone
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-73128DOI: 10.1016/j.bbrc.2004.07.092PubMedID: 15313187OAI: oai:DiVA.org:uu-73128DiVA: diva2:101039