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

Nobuo Suzuki, Masanori Somei, Kei Ichiro Kitamura, Russel J. Reiter, Atsuhiko Hattori

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)326-334
Number of pages9
JournalJournal of pineal research
Volume44
Issue number3
DOIs
StatePublished - Apr 1 2008

Keywords

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

ASJC Scopus subject areas

  • Endocrinology

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