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Vitamin A differentiall regulates RANKL and OPG expression in human osteoblasts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Osteoporos)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Osteoporos)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Osteoporos)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Osteoporos)
2004 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 322, no 1, 162-167 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Vitamin A, Osteoprotegerin, Bone resorption, Retinoic acid, Osteoporosis, Receptor for activation of NF-κB ligand, Retinoic acid receptor, RAR-antagonist, Osteoblast, Bone
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-73128DOI: 10.1016/j.bbrc.2004.07.092PubMedID: 15313187OAI: oai:DiVA.org:uu-73128DiVA: diva2:101039
Available from: 2005-05-31 Created: 2005-05-31Bibliographically approved

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Jacobson, AnnicaJohansson, SaraBranting, MariaMelhus, Håkan

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