Several reports indicate that melatonin is involved in the regulation of bone metabolism. To examine the direct effect of melatonin on osteoclasts and osteoblasts, we developed an in vitro assay using fish scales that contain osteoclasts, osteoblasts, and bone matrix, all of which are similar to those found in mammalian membrane bone. Using the assay, we demonstrated that melatonin suppressed osteoclastic and osteoblastic activities. These findings are in agreement with the reports from in vivo studies in mice and rats. In an attempt to develop molecules that increase bone mass, novel bromomelatonin derivatives were synthesized, and the effects of these chemicals on osteoclasts and osteoblasts using the scale assay were examined. As a result, novel bromomelatonin derivatives with the ability to possibly increase bone formation were identified. In scale osteoclasts, particularly, 1-benzyl-2,4,6-tribromomelatonin had a more potent activity than melatonin. In reference to osteoblasts, this agent (10(-9)-10(-6)M) significantly activated osteoblasts. The effect of 1-benzyl-2,4,6-tribromomelatonin on bone formation was confirmed in ovariectomized rats. Thus, the oral administration of 1-benzyl-2,4,6-tribromomelatonin augmented the total bone mineral density of the femoral metaphysis of ovariectomized rats. The stress-strain index of the diaphysis in 1-benzyl-2,4,6-tribromomelatonin-treated rats significantly increased in comparison with that in ovariectomized rats. In rats fed a low-calcium diet, the total bone mineral density of the femoral metaphysis significantly increased following the oral administration of 1-benzyl-2,4,6-tribromomelatonin. These studies identified a melatonin derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.

中文翻译：

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新型的褪黑激素衍生物可作为治疗骨病的潜在有效药物。

几篇报道表明褪黑激素参与了骨代谢的调节。为了检查褪黑素对破骨细胞和成骨细胞的直接作用，我们开发了一种体外试验，使用的鱼鳞中含有破骨细胞，成骨细胞和骨基质，所有这些都与哺乳动物膜骨中发现的相似。使用该测定法，我们证明了褪黑激素抑制了破骨细胞和成骨细胞的活性。这些发现与小鼠和大鼠体内研究的报告一致。为了开发增加骨骼质量的分子，合成了新的溴褪黑激素衍生物，并使用规模分析法检查了这些化学物质对破骨细胞和成骨细胞的作用。结果，鉴定了具有可能增加骨形成能力的新型溴褪黑激素衍生物。在大规模破骨细胞中，特别是1-苄基-2,4,6-三溴褪黑激素具有比褪黑激素更有效的活性。关于成骨细胞，该试剂（10（-9）-10（-6）M）显着激活了成骨细胞。在去卵巢的大鼠中证实了1-苄基-2,4,6-三溴褪黑激素对骨形成的影响。因此，口服1-苄基-2,4,6-三溴褪黑激素可增加去卵巢大鼠股骨干physi端的总骨矿物质密度。与去卵巢大鼠相比，经1-苄基-2,4,6-三溴褪黑激素处理的大鼠的骨干应力-应变指数显着增加。在低钙饮食的大鼠中，口服1-苄基-2,4,6-三溴褪黑激素后，股骨干physi端的总骨矿物质密度显着增加。