Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin

Masaki Nakano, Mika Ikegame, Junko Igarashi-Migitaka, Yusuke Maruyama, Nobuo Suzuki, Atsuhiko Hattori

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Many studies have investigated the actions of melatonin on osteoblasts and osteoclasts. However, the underlying mechanisms, especially regarding osteocyte function, remain largely unknown. Therefore, this study aimed to clarify the underlying mechanisms of melatonin action on bone tissue via osteocyte function. Chick calvariae were employed as a model. In ovo injection of melatonin (5, 50 and 500 μg) dose-dependently dec reased the mRNA expression levels of cathepsin K and matrix metallopro teinase 9 (MMP9) in chick calvariae without affecting the expression levels of recep tor activator of NF-κB ligand or osteoprotegerin. Surprisingly enough, the expression of calcitonin mRNA in chick calvariae was significantly raised. After 3 days of in vitro treatment of melatonin (10-7 and 10-5 M) on newly hatched chick calvariae, both calcitonin mRNA expr ession in calvariae and the concentration of calcitonin in cultured medium were augmented in a dose-dependent manner, coincident with the decreased mRNA expression levels of cathepsin K and MMP9. Immunohistochemical analyses revealed expression of melatonin receptors and calcitonin by osteocytes buried in bone matrix. Moreover, the mRNA expression levels of melatonin receptors, calcitonin and sclerostin (a marker of osteocyte), were strongly and positively correlated. In conclus ion, we demonstrated the expression of melatonin receptors and calcitonin expression in osteocytes for the first time and suggest a new mechanism underlying the suppressive effect of melatonin on osteoclasts via upregulation of calcitonin secretion by osteocytes.

Original languageEnglish
Pages (from-to)13-23
Number of pages11
JournalJournal of Endocrinology
Issue number2
Publication statusPublished - Aug 2019


  • Calcitonin
  • Melatonin
  • Melatonin receptor
  • Osteoclast
  • Psteocyte

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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