Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels.
Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels.
复制标题
硝酸镓调节大鼠成骨细胞骨钙素蛋白表达和 mRNA 水平。
DOI：
10.1002/jbmr.5650080113
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Bockman,RS
中科院分区：
文献类型：
--
作者：
GuidonJr,PT;Salvatori,R;Bockman,RS
已发现硝酸镓（一种IIIa族金属盐）在临床上可有效治疗癌症相关高钙血症和佩吉特病的加速骨吸收。在这里，我们报告了硝酸镓对大鼠成骨细胞样细胞系ROS 17/2.8上骨钙素mRNA和蛋白水平的影响。硝酸镓使培养基中的组成型和维生素D3刺激的骨钙素蛋白水平降低一半，骨钙素mRNA水平降低至对照的三分之一到十分之一。硝酸镓还抑制维生素D3刺激骨钙素和骨桥蛋白mRNA水平，但不影响组成性骨桥蛋白mRNA水平。在几种不同的金属检查，镓是独特的能力，降低骨钙素mRNA水平，而不降低其他mRNA的ROS 17/2.8细胞合成的水平。硝酸镓对骨钙素mRNA和蛋白质合成的影响类似于ROS 17/2.8细胞暴露于转化生长因子β1（TGFβ1）时所观察到的效果;然而，在硝酸镓处理的ROS 17/2.8细胞培养基中未检测到TGF-β 1。使用RNA聚合酶II抑制剂5，6-二氯-1-β-D-呋喃核糖基苯并咪唑证明硝酸镓不会改变骨钙素mRNA的稳定性。瞬时转染实验中使用大鼠骨钙素启动子连接到细菌报告基因氯霉素乙酰转移酶表明，硝酸镓阻断报告基因的表达刺激骨钙素启动子。这是第一次报道硝酸镓对分离的成骨细胞的影响。
Gallium nitrate, a group IIIa metal salt, has been found to be clinically effective for the treatment of accelerated bone resorption in cancer‐related hypercalcemia and Paget's disease. Here we report the effects of gallium nitrate on osteocalcin mRNA and protein levels on the rat osteoblast‐like cell line ROS 17/2.8. Gallium nitrate reduced both constitutive and vitamin D3‐stimulated osteocalcin protein levels in culture medium by one‐half and osteocalcin mRNA levels to one‐third to one‐tenth of control. Gallium nitrate also inhibited vitamin D3stimulation of osteocalcin and osteopontin mRNA levels but did not affect constitutive osteopontin mRNA levels. Among several different metals examined, gallium was unique in its ability to reduce osteocalcin mRNA levels without decreasing levels of other mRNAs synthesized by ROS 17/2.8 cells. The effects of gallium nitrate on osteocalcin mRNA and protein synthesis mimic those seen when ROS 17/2.8 cells are exposed to transforming growth factor β1(TGFβ1); however, TGF‐β1was not detected in gallium nitratetreated ROS 17/2.8 cell media. Use of the RNA polymerase II inhibitor 5,6‐dichloro‐1‐β‐D‐ribofuranosylbenzimidazole demonstrated that gallium nitrate did not alter the stability of osteocalcin mRNA. Transient transfection assays using the rat osteocalcin promoter linked to the bacterial reporter gene chloramphenicol acetyltransferase indicated that gallium nitrate blocked reporter gene expression stimulated by the osteocalcin promoter. This is the first reported effect of gallium nitrate on isolated osteoblast cells.