Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture
Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture
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DOI：
10.1007/s007740050071
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发表时间：
1999
影响因子：
3.3
通讯作者：
Y. Koshihara;Shunji Kodama;H. Ishibashi;Y. Azuma;T. Ohta;S. Karube
中科院分区：
文献类型：
--
作者：
Y. Koshihara;Shunji Kodama;H. Ishibashi;Y. Azuma;T. Ohta;S. Karube
阿仑膦酸钠是一种治疗恶性肿瘤和骨质疏松症高钙血症的有效药物，最近被开发用于治疗恶性肿瘤高钙血症。在这项研究中，延时电影显微摄影术被用来调查这种代理人的形态和人破骨细胞样多核细胞（MNCs）的运动的影响，从人骨髓。10− 5 M的阿仑膦酸钠在加入后7.5 h开始诱导细胞收缩。在去除阿仑膦酸钠后立即显著诱导收缩。然而，收缩几乎消失后18小时，和破骨细胞样MNCs恢复其原来的大小和形状。在10− 4 M时，阿仑膦酸钠治疗后收缩仅部分恢复。相比之下，未处理的对照细胞在用培养基洗涤后没有改变其形态。运动分析显示，用10− 5 M阿仑膦酸钠处理的破骨细胞样MNCs在洗涤后运动活跃，但在10− 4 M时运动轨迹非常狭窄。在10− 4 M时，细胞中的肌动蛋白环开始分解，在加入后6 h开始。阿仑膦酸钠对人破骨细胞样MNCs形态和运动的影响在10− 5 M时是可逆的，这表明阿仑膦酸钠在高达10− 5 M（这是骨吸收的有效剂量）时不会对人破骨细胞造成任何细胞损伤。
Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10−5M induced contraction of the cells starting 7.5 h after its addition. contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18 h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10−4M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10−5M alendronate moved actively after washing, but at 10−4M the motility locus was very narrow. At 10−4M, the actin ring in the cells began to break down, beginning 6 h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10−5M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10−5M, which is an effective dose for bone resorption.