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Updated: Jan 25, 2026
Obtaining Primary Osteocytes Through Murine Calvarial Fractionation of GFP-Expressing Osteocytes
Published on: June 2, 2020
Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin
Masaki Nakano1,2, Mika Ikegame3, Junko Igarashi-Migitaka4
1Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, Chiba, Japan.
Abstract:
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.
Insights
Melatonin significantly impacts bone health by upregulating calcitonin in osteocytes, a novel mechanism that suppresses osteoclast activity. This research clarifies melatonin
Area of Science:
- Bone Biology
- Endocrinology
- Cellular Mechanisms
Background:
- Melatonin's effects on osteoblasts and osteoclasts are known, but its role in osteocyte function is unclear.
- Osteocytes, embedded within the bone matrix, play a crucial role in bone remodeling and mechanotransduction.
- Understanding melatonin's osteocyte-specific mechanisms is vital for elucidating its broader skeletal effects.
Purpose of the Study:
- To investigate the mechanisms of melatonin action on bone tissue, focusing on osteocyte function.
- To clarify the dose-dependent effects of melatonin on specific gene expressions related to bone metabolism.
- To identify the presence and role of melatonin receptors and calcitonin within osteocytes.
Main Methods:
- Chick calvariae were used as an in vivo and in vitro model system.
- Melatonin was administered via in ovo injection and in vitro culture.
- Gene expression (cathepsin K, MMP9, receptor activator of NF-κB ligand, osteoprotegerin, calcitonin, melatonin receptors, sclerostin) and protein concentration (calcitonin) were analyzed.
- Immunohistochemistry was employed to detect protein expression in osteocytes.
Main Results:
- Melatonin dose-dependently decreased cathepsin K and matrix metalloproteinase 9 (MMP9) mRNA expression.
- Melatonin significantly increased calcitonin mRNA expression and protein secretion in a dose-dependent manner.
- Osteocytes were found to express both melatonin receptors and calcitonin.
- Positive correlations were observed between melatonin receptors, calcitonin, and sclerostin mRNA expression in osteocytes.
Conclusions:
- This study demonstrates, for the first time, the expression of melatonin receptors and calcitonin in osteocytes.
- Melatonin suppresses osteoclast activity potentially through the upregulation of calcitonin secretion by osteocytes.
- A novel mechanism for melatonin's skeletal effects involving osteocyte-mediated calcitonin regulation is proposed.
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