Melatonin is a potential drug for the prevention of bone loss during space flight
Melatonin is a potential drug for the prevention of bone loss during space flight
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DOI：
10.1111/jpi.12594
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发表时间：
2019-07-19
影响因子：
10.3
通讯作者：
Suzuki, Nobuo
中科院分区：
文献类型：
--
作者：
Ikegame, Mika;Hattori, Atsuhiko;Suzuki, Nobuo
宇航员在太空飞行期间由于微重力条件而经历骨质疏松症样的骨质流失。为了防止骨质流失，他们需要一种无风险的抗吸收药物。据报道，褪黑激素抑制破骨细胞功能。然而，没有研究审查褪黑激素对微重力条件下骨代谢的影响。我们使用金鱼鳞片作为破骨细胞和成骨细胞共存的骨模型，并证明乙酰血清素O-甲基转移酶（褪黑激素合成所必需的酶）的mRNA表达水平在微重力下显著下降。在空间飞行期间，微重力刺激了骨细胞活性，并显著增加了破骨细胞分化和活化的基因表达。褪黑激素治疗显着刺激降钙素（破骨细胞抑制激素）mRNA的表达，并降低核因子κ B受体激活剂配体（破骨细胞生成的启动子）的mRNA表达，这与破骨细胞功能的抑制基因表达水平相一致。这是第一项研究报告褪黑激素对微重力下骨细胞活化的抑制作用。我们还观察到褪黑激素通过增加降钙素分泌对破骨细胞的新作用途径。褪黑激素可能是一种潜在的新型药物的来源，以防止在太空飞行期间的骨丢失。
Astronauts experience osteoporosis-like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O-methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast-inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor kappa B ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.