Vitamin A differentially regulates RANKL and OPG expression in human osteoblasts

被引:38
作者
Jacobson, A [1 ]
Johansson, S [1 ]
Branting, M [1 ]
Melhus, H [1 ]
机构
[1] Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden
关键词
vitamin A; osteoprotegerin; bone resorption retinoic acid; osteoporosis; receptor for activation of NF-kappa B ligand; retinoic acid receptor; RAR-antagonist; osteoblast; bone;
D O I
10.1016/j.bbrc.2004.07.092
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 4 h (-68%) in primary cultures and after 8 h (-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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:162 / 167
页数:6
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