Novel bromomelatonin derivatives suppress osteoclastic activity and increase osteoblastic activity: Implications for the treatment of bone diseases

• Suzuki, Nobuo

• Somei, Masanori

• Kitamura, Keiichiro

• Reiter, Russel J.

• Hattori, Atsuhiko

抄録

金沢大学環日本海域環境研究センター生物多様性研究部門

The teleost scale is a calcified tissue that contains osteoclasts, osteoblasts, and bone matrix, all of which are similar to those found in mammalian membrane bone. Using the goldfish scale, we recently developed a new in vitro assay system and previously demonstrated that melatonin suppressed both osteoclastic and osteoblastic activities in this assay system. In mammals, 2-bromomelatonin possesses a higher affinity for the melatonin receptor than does melatonin. Using a newly developed synthetic method, we synthesized 2-bromomelatonin, 2,4,6-tribromomelatonin and novel bromomelatonin derivatives (1-allyl-2,4,6-tribromomelatonin, 1-propargyl-2,4,6-tribromomelatonin, 1-benzyl-2,4,6-tribromomelatonin, and 2,4,6,7-tetrabromomelatonin) and then examined the effects of these chemicals on osteoclasts and osteoblasts. All bromomelatonin derivatives, as well as melatonin, had an inhibitory action on osteoclasts. In particular, 1-benzyl-2,4,6-tribromomelatonin (benzyl-tribromomelatonin) possessed a stronger activity than melatonin. At an in vitro concentration of 10-10 m, benzyl-tribromomelatonin still suppressed osteoclastic activity after 6 hr of incubation. In reference to osteoblasts, all bromomelatonin derivatives had a stimulatory action, although melatonin inhibited osteoblastic activity. In addition, estrogen receptor mRNA expression (an osteoblastic marker) was increased in benzyl-tribromomelatonin (10-7 m)-treated scales. Taken together, the present results strongly suggest that these novel melatonin derivatives have significant potential for use as beneficial drug for bone diseases such as osteoporosis. © 2007 The Authors. 全文公開200904

収録刊行物

• Journal of Pineal Research

  Journal of Pineal Research 44 (3), 326-334, 2008-04-01

  Blackwell Publishing

キーワード

• Bone diseases
• Bromomelatonin derivatives
• Goldfish
• Osteoblasts
• Osteoclasts
• Scales

詳細情報

• CRID: 1050282810963603456
• NII論文ID: 120001170120
• NII書誌ID: AA10641255
• ISSN: 07423098
• Web Site: http://hdl.handle.net/2297/17120
• 本文言語コード: en
• 資料種別: journal article
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