Long-term effects of neridronate on human osteoblastic cell cultures
Long-term effects of neridronate on human osteoblastic cell cultures
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DOI：
10.1016/j.bone.2004.06.001
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发表时间：
2004-10-01
期刊：
影响因子：
4.1
通讯作者：
Marcolongo, R
中科院分区：
文献类型：
--
作者：
Frediani, B;Spreafico, A;Marcolongo, R
双膦酸盐（BP）广泛用于治疗各种骨相关疾病，特别是骨转换偏向骨质溶解的疾病。BP直接作用于破骨细胞减少骨吸收的机制现在已经在分子水平上得到了很大程度的阐明。关于BP对成骨细胞影响的研究显示了不同的结果。许多体外研究已经报道了几种BP对成骨细胞增殖和矿化的积极作用，然而，观察到的作用不同，这取决于所使用的各种不同的模型系统。目标.我们已经研究了奈立膦酸盐，一种适用于胃肠外给药的氨基二膦酸盐，是否会对体外人成骨细胞增殖和分化产生影响。方法.我们研究了在从14种不同骨标本中获得的不同人成骨细胞培养物中长期添加奈立膦酸盐（10（-3）至10（-11）M）是否会影响细胞数量、内源性细胞碱性磷酸酶（ALKP）活性和矿化结节的形成。结果我们的研究结果表明，奈立膦酸盐在体外不会对正常人成骨细胞的活力、增殖和细胞活性产生负面影响，即使在长期（20天）加入浓度等于或低于10（-5）mol/l（治疗剂量）的药物后也是如此。此外，奈立膦酸盐似乎可以增强培养的成骨细胞在成熟骨形成细胞中的分化。在用奈立膦酸盐10（-8）M处理的培养物中观察到碱性磷酸酶活性（10天后+50%; P < 0.01）和矿化结节（20天后+48%; P < 0.05）的最大增加。结论.这些结果鼓励在脱矿代谢性骨疾病的长期治疗中使用奈立膦酸盐。(C)2004年爱思唯尔公司All rights reserved.
Bisphosphonates (BP's) are widely used in the treatment of a variety of bone-related diseases, particularly where the bone turnover is skewed in favor of osteolysis. The mechanisms by which BP's reduce bone resorption directly acting oil osteoclasts are now largely clarified even at molecular level. Researches concerning the BP's effects on osteoblast have instead shown variable results. Many in vitro studies have reported positive effects on osteoblasts proliferation and mineralization for several BPs, however, the observed effects differ, depending on the variety of different model system that has been used. Objectives. We have investigated if neridronate, an aminobisphosphonate suitable for pulsatory parenteral administration, could have an effect on human osteoblastic proliferation and differentiation in vitro. Methods. We have investigated whether prolonged addition of neridronate (from 10(-3) to 10(-11) M) to different human osteoblasts cultures, obtained from 14 different bone specimens, could affect the cells number, the endogenous cellular alkaline phosphatase (ALKP) activity, and the formation of mineralized nodules. Results. Our results show that neridronate does not negatively affect in vitro the viability, proliferation, and cellular activity of normal human osteoblasts even after a long period addition of the drug (20 days) at concentrations equal or lower than 10(-5) mol/l (therapeutic dose). In addition, neridronate seems to enhance the differentiation of cultured osteoblasts in mature bone-forming cells. A maximum increase of alkaline phosphatase activity (+50% after 10 days; P < 0.01) and mineralized nodules (+48% after 20 days; P < 0.05) was observed in cultures treated with neridronate 10(-8) M. Conclusions. These results encourage the use of neridronate in long-term therapy of demineralizing metabolic bone disorders. (C) 2004 Elsevier Inc. All rights reserved.