Jacobson A, Johansson S, Branting M, Melhus H
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
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.
全反式维甲酸（ATRA）可诱导骨吸收，但其分子机制尚不清楚。我们研究了ATRA对人MG-63骨肉瘤细胞和成骨细胞样原代培养物中骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）表达的影响。ATRA以剂量依赖的方式下调MG-63细胞中OPG的蛋白水平，在10(-6)M剂量时观察到最大降幅（-56%）。定量实时PCR证实了这种效应，在原代培养物中4小时后OPG mRNA下降（-68%），在MG-63细胞中8小时后下降（-87%）。视黄酸受体（RAR）拮抗剂可抑制OPG表达的降低，而RARβ,γ激动剂可模拟这种降低，表明ATRA的作用是由这些受体介导的。在原代培养物中，我们发现RANKL mRNA表达增加了三倍。因此，RANKL/OPG比值显著升高，提示了ATRA诱导骨吸收的潜在机制。
