TY - JOUR
T1 - Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin
AU - Nakano, Masaki
AU - Ikegame, Mika
AU - Igarashi-Migitaka, Junko
AU - Maruyama, Yusuke
AU - Suzuki, Nobuo
AU - Hattori, Atsuhiko
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Number JP18K11016, JP16K11442 and JP16K07871, and Grant-in-Aid for Scientific Research at Tokyo Medical and Dental University.
Funding Information:
This work was supported by JSPS KAKENHI Grant Number JP18K11016,
Publisher Copyright:
© 2019 Society for Endocrinology.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
KW - Calcitonin
KW - Melatonin
KW - Melatonin receptor
KW - Osteoclast
KW - Psteocyte
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U2 - 10.1530/JOE-18-0707
DO - 10.1530/JOE-18-0707
M3 - Article
C2 - 31042672
AN - SCOPUS:85077728335
VL - 242
SP - 13
EP - 23
JO - Journal of Endocrinology
JF - Journal of Endocrinology
SN - 0022-0795
IS - 2
ER -