Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin

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 osteocy...

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Veröffentlicht in:Journal of endocrinology 2019-08, Vol.242 (2), p.13-23
Hauptverfasser: Nakano, Masaki, Ikegame, Mika, Igarashi-Migitaka, Junko, Maruyama, Yusuke, Suzuki, Nobuo, Hattori, Atsuhiko
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container_issue 2
container_start_page 13
container_title Journal of endocrinology
container_volume 242
creator Nakano, Masaki
Ikegame, Mika
Igarashi-Migitaka, Junko
Maruyama, Yusuke
Suzuki, Nobuo
Hattori, Atsuhiko
description 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 decreased the mRNA expression levels of cathepsin K and matrix metalloproteinase 9 (MMP9) in chick calvariae without affecting the expression levels of receptor 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 expression 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 conclusion, 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.
doi_str_mv 10.1530/JOE-18-0707
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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 decreased the mRNA expression levels of cathepsin K and matrix metalloproteinase 9 (MMP9) in chick calvariae without affecting the expression levels of receptor 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 expression 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. 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subjects Animals
Avian Proteins - genetics
Avian Proteins - metabolism
Calcitonin - genetics
Calcitonin - metabolism
Cells, Cultured
Chick Embryo
Chickens
Gene Expression Regulation, Developmental - drug effects
Melatonin - administration & dosage
Melatonin - pharmacology
Osteoclasts - cytology
Osteoclasts - drug effects
Osteoclasts - metabolism
Osteocytes - cytology
Osteocytes - drug effects
Osteocytes - metabolism
Receptors, Melatonin - genetics
Receptors, Melatonin - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Skull - cytology
Skull - drug effects
Skull - metabolism
Up-Regulation - drug effects
title Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin
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