Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line.
Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line.
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DOI：
10.1054/bjoc.2000.1679
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发表时间：
2001-04-06
影响因子：
8.8
通讯作者：
Choong PF
中科院分区：
文献类型：
--
作者：
Mackie PS;Fisher JL;Zhou H;Choong PF
骨肉瘤的局部生长包括通过蛋白分解机制和/或宿主破骨细胞激活来破坏宿主骨。破骨细胞的形成和活性受成骨细胞来源的因子调节，如破骨细胞分化因子、核因子受体激活剂B配体(RANKL)和骨保护素抑制物(OPG)等。我们研究了双膦酸盐对克隆性大鼠骨肉瘤细胞系的体外作用。向UMR106-01细胞培养物(10−8M~10−4M，最长5天)中加入氨基双膦酸帕米磷酸酯。给药时间相同(10−6M~10−2M)。检测细胞增殖、凋亡及基因表达。两种药物均以时间和剂量依赖的方式抑制细胞增殖。ELISA分析显示DNA片段化增加，尽管在所研究的剂量之间没有显着的剂量相关差异。双膦酸盐处理的培养物有更多的细胞亚群，表现出凋亡的形态变化。两种药物均可下调骨桥蛋白和RANKLmRNA的表达，而对碱性磷酸酶、前α1(I)胶原和成骨细胞生长因子的表达无明显影响。体外实验表明，双膦酸类化合物不仅对骨肉瘤细胞的生长和凋亡有直接作用，而且可能通过改变破骨细胞调节因子的相对表达，抑制破骨细胞的活性及其募集。©2001癌症研究活动http://www.bjcancer.com
Local growth of osteosarcoma involves destruction of host bone by proteolytic mechanisms and/or host osteoclast activation. Osteoclast formation and activity are regulated by osteoblast-derived factors such as the osteoclast differentiating factor, receptor activator of NF-κB ligand (RANKL) and the inhibitor osteoprotegerin (OPG). We have investigated the in vitro effects of bisphosphonates on a clonal rat osteosarcoma cell line. The aminobisphosphonate pamidronate was added to UMR 106-01 cell cultures (10−8M to 10−4M up to 5 days). The non-aminobisphosphonate clodronate was administered for the same time periods (10−6M to 10−2M). Cell proliferation, apoptosis and mRNA expression was assessed. Both agents inhibited cell proliferation in a time- and dose-dependent manner. ELISA analysis demonstrated an increase in DNA fragmentation although there was no significant dose-related difference between the doses studied. Bisphosphonate-treated cultures had a greater subpopulation of cells exhibiting morphological changes of apoptosis. Expression of mRNA for osteopontin and RANKL was down-regulated by both agents, while the expression of mRNA for alkaline phosphatase, pro-α1(I) collagen and OPG was not altered. Out in vitro work suggests the bisphosphonates not only have direct effects on osteosarcoma cell growth and apoptosis, but also, by altering the relative expression of osteoclast-regulating factors, they may inhibit the activity of osteoclasts and their recruitment. © 2001 Cancer Research Campaignhttp://www.bjcancer.com
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影响因子：
6.2
作者：
Luckman, SP;Hughes, DE;Rogers, MJ
通讯作者：
Rogers, MJ
影响因子：
4.1
作者：
GOZIOTIS, A;SUKHU, B;TENENBAUM, HC
通讯作者：
TENENBAUM, HC
DOI：
10.1016/s0169-6009(08)80055-4
发表时间：
1994-08-01
期刊：
BONE AND MINERAL
影响因子：
--
作者：
EVANS, CE;BRAIDMAN, IP
通讯作者：
BRAIDMAN, IP
影响因子：
64.8
作者：
MARTIN, TJ;INGLETON, PM;MELICK, RA
通讯作者：
MELICK, RA
影响因子：
6.2
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
通讯作者：
Manolagas, SC