Biological Effects of Anti-RANKL Antibody and Zoledronic Acid on Growth and Tooth Eruption in Growing Mice

Biological Effects of Anti-RANKL Antibody and Zoledronic Acid on Growth and Tooth Eruption in Growing Mice
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DOI:
10.1038/s41598-019-56151-1
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发表时间:
2019-12-27
期刊:
影响因子:
4.6
通讯作者:
Takami, Masamichi
Takami, Masamichi
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Isawa, Motoki;Karakawa, Akiko;Takami, Masamichi

文献摘要

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抗骨吸收药物狄诺塞单抗(一种抗人RANKL抗体)和唑来膦酸(ZOL)(一种含氮双膦酸盐)最近已被用于治疗儿童骨病患者,但有关其在生长期儿童中的作用的细节尚未完全阐明。在本研究中,我们从1周龄开始对小鼠给予这些抗吸收药物,并继续每周注射一次,共注射7次。接受抗RANKL抗体的小鼠显示正常生长和牙齿萌出,尽管注意到长骨和牙槽骨中的骨硬化性骨体积增加,但几乎没有破骨细胞,观察到正常数量的成骨细胞。与此相反,ZOL显着延迟身体生长,牙根形成,牙齿萌出,破骨细胞增加,成骨细胞数量减少。这些发现表明,某些类型的抗吸收药物通过成骨细胞分化调节牙齿萌出。
The anti-bone resorptive drugs denosumab, an anti-human-RANKL antibody, and zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, have recently been applied for treatment of pediatric patients with bone diseases, though details regarding their effects in growing children have yet to be fully elucidated. In the present study, we administered these anti-resorptive drugs to mice from the age of 1 week and continued once-weekly injections for a total of 7 times. Mice that received the anti-RANKL antibody displayed normal growth and tooth eruption, though osteopetrotic bone volume gain in long and alveolar bones was noted, while there were nearly no osteoclasts and a normal of number osteoblasts observed. In contrast, ZOL significantly delayed body growth, tooth root formation, and tooth eruption, with increased osteoclast and decreased osteoblast numbers. These findings suggest regulation of tooth eruption via osteoblast differentiation by some types of anti-resorptive drugs.