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Melatonin is a potential drug for the prevention of bone loss during space flight.

ABSTRACT: 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 ?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.

SUBMITTER: Ikegame M

PROVIDER: S-EPMC6771646 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Melatonin is a potential drug for the prevention of bone loss during space flight.

Ikegame Mika M Hattori Atsuhiko A Tabata Makoto J MJ Kitamura Kei-Ichiro KI Tabuchi Yoshiaki Y Furusawa Yukihiro Y Maruyama Yusuke Y Yamamoto Tatsuki T Sekiguchi Toshio T Matsuoka Risa R Hanmoto Taizo T Ikari Takahiro T Endo Masato M Omori Katsunori K Nakano Masaki M Yashima Sayaka S Ejiri Sadakazu S Taya Toshiki T Nakashima Hiroshi H Shimizu Nobuaki N Nakamura Masahisa M Kondo Takashi T Hayakawa Kazuichi K Takasaki Ichiro I Kaminishi Atsushi A Akatsuka Ryosuke R Sasayama Yuichi Y Nishiuchi Takumi T Nara Masayuki M Iseki Hachiro H Chowdhury Vishwajit S VS Wada Shigehito S Ijiri Kenichi K Takeuchi Toshio T Suzuki Tohru T Ando Hironori H Matsuda Kouhei K Somei Masanori M Mishima Hiroyuki H Mikuni-Takagaki Yuko Y Funahashi Hisayuki H Takahashi Akihisa A Watanabe Yoshinari Y Maeda Masahiro M Uchida Hideaki H Hayashi Akio A Kambegawa Akira A Seki Azusa A Yano Sachiko S Shimazu Toru T Suzuki Hiromi H Hirayama Jun J Suzuki Nobuo N

Journal of pineal research 20190719 3

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-methylt ...[more]

PMID: 31286565

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Project description:Astronauts are inevitably exposed to two major risks during space flight, microgravity and radiation. Exposure to microgravity has been discovered to lead to rapid and vigorous bone loss due to elevated osteoclastic activity. In addition, long‑term exposure to low‑dose‑rate space radiation was identified to promote DNA damage accumulation that triggered chronic inflammation, resulting in an increased risk for bone marrow suppression and carcinogenesis. In our previous study, melatonin, a hormone known to regulate the sleep‑wake cycle, upregulated calcitonin expression levels and downregulated receptor activator of nuclear factor‑κB ligand expression levels, leading to improved osteoclastic activity in a fish scale model. These results indicated that melatonin may represent a potential drug or lead compound for the prevention of bone loss under microgravity conditions. However, it is unclear whether melatonin affects the biological response induced by space radiation. The aim of the present study was to evaluate the effect of melatonin on the expression levels of genes responsive to space radiation. In the present study, to support the previous data regarding de novo transcriptome analysis of goldfish scales, a detailed and improved experimental method (e.g., PCR duplicate removal followed by de novo assembly, global normalization and calculation of statistical significance) was applied for the analysis. In addition, the transcriptome data were analyzed via global normalization, functional categorization and gene network construction to determine the impact of melatonin on gene expression levels in irradiated fish scales cultured in space. The results of the present study demonstrated that melatonin treatment counteracted microgravity‑ and radiation‑induced alterations in the expression levels of genes associated with DNA replication, DNA repair, proliferation, cell death and survival. Thus, it was concluded that melatonin may promote cell survival and ensure normal cell proliferation in cells exposed to space radiation.

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Melatonin is a potential drug for the prevention of bone loss during space flight.

Publications

Melatonin is a potential drug for the prevention of bone loss during space flight.

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