Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin
Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin
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DOI：
10.1530/joe-18-0707
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Hattori, Atsuhiko
中科院分区：
文献类型：
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作者：
Nakano, Masaki;Ikegame, Mika;Hattori, Atsuhiko
许多研究已经研究了褪黑素对成骨细胞和破骨细胞的作用。然而，潜在的机制，特别是关于骨细胞的功能，在很大程度上仍然不清楚。因此，本研究旨在阐明褪黑素通过骨细胞功能作用于骨组织的潜在机制。以雏鸡头盖骨为模型。静脉注射褪黑素(5、50和500 mg)可剂量依赖性地降低鸡颅盖骨组织蛋白酶K和基质金属蛋白酶9(MMP9)的mRNA表达水平，但不影响核因子-kappaB受体激活物配体或护骨素的表达水平。令人惊讶的是，雏鸡头盖骨中降钙素mRNA的表达显著上调。褪黑素(10(-7)和10(-5)M)体外处理新孵化的雏鸡颅骨3d后，颅骨组织降钙素mRNA表达和培养液中降钙素浓度均呈剂量依赖性增加，与组织蛋白酶K和MMP9mRNA表达水平下降相一致。免疫组织化学分析显示，骨基质中的骨细胞表达褪黑素受体和降钙素。此外，褪黑激素受体、降钙素和硬化素(骨细胞的标志物)的mRNA表达水平呈显著正相关。综上所述，我们首次证实了褪黑素受体和降钙素在骨细胞中的表达，并提出了褪黑素通过上调骨细胞分泌降钙素抑制破骨细胞的新机制。
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 mu g) 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-kappa B 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.