Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo
Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo
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DOI：
10.1111/j.1600-079x.2006.00410.x
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发表时间：
2007-04-01
影响因子：
10.3
通讯作者：
Nagayama, Masaru
中科院分区：
文献类型：
--
作者：
Satomura, Kazuhito;Tobiume, Satoru;Nagayama, Masaru
褪黑素可以调节多种生理过程，包括控制昼夜节律、调节季节性生殖功能、调节体温等。在啮齿动物和鸡身上进行的体外和体内实验中积累的证据也表明，褪黑激素可能对骨骼生长和骨骼形成有影响。然而，关于褪黑素对人类成骨细胞的影响知之甚少，因此仍有待阐明。本研究旨在确定褪黑激素是否能影响体外人成骨细胞的增殖和分化，并证明褪黑激素可作为药物剂用于缩短骨折、各种截骨术和骨牵引治疗期的可能性。逆转录聚合酶链反应和Western blot分析表明，人成骨细胞表达褪黑素I a受体，其表达水平随着宿主年龄的增长而逐渐降低。褪黑素在一定药理学浓度下刺激人成骨细胞增殖和碱性磷酸酶活性呈剂量依赖性。褪黑素还以剂量依赖的方式促进I型胶原、骨桥蛋白、骨涎蛋白和骨钙素的基因表达，并在体外刺激矿化基质的形成。此外，小鼠腹腔注射褪黑素增加了新形成的股骨皮质骨的体积。这些结果表明，褪黑素可以直接促进人、啮齿动物和鸡成骨细胞的分化，也提示褪黑素可以作为促进骨再生的药物。
Melatonin is known to regulate a variety of physiological processes including, control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, and so forth. Accumulating evidence from in vitro and in vivo experiments using rodent and chicken has also suggested that melatonin may have an influence on skeletal growth and bone formation. However, little is known about the effects of melatonin on human osteoblasts, which thus remains to be elucidated. This study was performed to determine whether melatonin could affect the proliferation and differentiation of human osteoblasts in vitro and to demonstrate the possibility that melatonin could be applied as a pharmaceutical agent to shorten the treatment period of bone fracture, various osteotomies, and bone distraction. Reverse transcription-polymerase chain reaction and Western blot analysis showed that human osteoblasts expressed melatonin I a receptor and that its expression levels decreased gradually with the age of the hosts. Melatonin stimulated the proliferation and alkaline phosphatase activity of human osteoblasts in a dose-dependent manner at the pharmacological concentrations. Melatonin also promotes gene expression of type I collagen, osteopontin, bone sialoprotein, and osteocalcin in a dose-dependent manner, and stimulated the mineralized matrix formation in vitro. Moreover, intraperitoneal administration of melatonin to mice increased the volume of newly formed cortical bone of femora. These results demonstrated that melatonin directly accelerated the differentiation of osteoblasts of human as well as rodent and chicken and also suggested that melatonin could be applied as a pharmaceutical agent to promote bone regeneration.