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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 κB 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.

Original languageEnglish
Article numbere12594
JournalJournal of Pineal Research
Volume67
Issue number3
DOIs
Publication statusPublished - Oct 1 2019

Fingerprint

Space Flight
Melatonin
Osteoclasts
Weightlessness
Bone and Bones
Pharmaceutical Preparations
Messenger RNA
Acetylserotonin O-Methyltransferase
Bone Density Conservation Agents
Astronauts
Gene Expression
Goldfish
Calcitonin
Cytoplasmic and Nuclear Receptors
Osteoblasts
Osteogenesis
Osteoporosis
Hormones
Ligands
Enzymes

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Ikegame, M., Hattori, A., Tabata, M. J., Kitamura, K. I., Tabuchi, Y., Furusawa, Y., ... Suzuki, N. (2019). Melatonin is a potential drug for the prevention of bone loss during space flight. Journal of Pineal Research, 67(3), [e12594]. https://doi.org/10.1111/jpi.12594

Melatonin is a potential drug for the prevention of bone loss during space flight. / Ikegame, Mika; Hattori, Atsuhiko; Tabata, Makoto J.; Kitamura, Kei ichiro; Tabuchi, Yoshiaki; Furusawa, Yukihiro; Maruyama, Yusuke; Yamamoto, Tatsuki; Sekiguchi, Toshio; Matsuoka, Risa; Hanmoto, Taizo; Ikari, Takahiro; Endo, Masato; Omori, Katsunori; Nakano, Masaki; Yashima, Sayaka; Ejiri, Sadakazu; Taya, Toshiki; Nakashima, Hiroshi; Shimizu, Nobuaki; Nakamura, Masahisa; Kondo, Takashi; Hayakawa, Kazuichi; Takasaki, Ichiro; Kaminishi, Atsushi; Akatsuka, Ryosuke; Sasayama, Yuichi; Nishiuchi, Takumi; Nara, Masayuki; Iseki, Hachiro; Chowdhury, Vishwajit S.; Wada, Shigehito; Ijiri, Kenichi; Takeuchi, Toshio; Suzuki, Tohru; Ando, Hironori; Matsuda, Kouhei; Somei, Masanori; Mishima, Hiroyuki; Mikuni-Takagaki, Yuko; Funahashi, Hisayuki; Takahashi, Akihisa; Watanabe, Yoshinari; Maeda, Masahiro; Uchida, Hideaki; Hayashi, Akio; Kambegawa, Akira; Seki, Azusa; Yano, Sachiko; Shimazu, Toru; Suzuki, Hiromi; Hirayama, Jun; Suzuki, Nobuo.

In: Journal of Pineal Research, Vol. 67, No. 3, e12594, 01.10.2019.

Research output: Contribution to journalArticle

Ikegame, M, Hattori, A, Tabata, MJ, Kitamura, KI, Tabuchi, Y, Furusawa, Y, Maruyama, Y, Yamamoto, T, Sekiguchi, T, Matsuoka, R, Hanmoto, T, Ikari, T, Endo, M, Omori, K, Nakano, M, Yashima, S, Ejiri, S, Taya, T, Nakashima, H, Shimizu, N, Nakamura, M, Kondo, T, Hayakawa, K, Takasaki, I, Kaminishi, A, Akatsuka, R, Sasayama, Y, Nishiuchi, T, Nara, M, Iseki, H, Chowdhury, VS, Wada, S, Ijiri, K, Takeuchi, T, Suzuki, T, Ando, H, Matsuda, K, Somei, M, Mishima, H, Mikuni-Takagaki, Y, Funahashi, H, Takahashi, A, Watanabe, Y, Maeda, M, Uchida, H, Hayashi, A, Kambegawa, A, Seki, A, Yano, S, Shimazu, T, Suzuki, H, Hirayama, J & Suzuki, N 2019, 'Melatonin is a potential drug for the prevention of bone loss during space flight', Journal of Pineal Research, vol. 67, no. 3, e12594. https://doi.org/10.1111/jpi.12594
Ikegame M, Hattori A, Tabata MJ, Kitamura KI, Tabuchi Y, Furusawa Y et al. Melatonin is a potential drug for the prevention of bone loss during space flight. Journal of Pineal Research. 2019 Oct 1;67(3). e12594. https://doi.org/10.1111/jpi.12594
Ikegame, Mika ; Hattori, Atsuhiko ; Tabata, Makoto J. ; Kitamura, Kei ichiro ; Tabuchi, Yoshiaki ; Furusawa, Yukihiro ; Maruyama, Yusuke ; Yamamoto, Tatsuki ; Sekiguchi, Toshio ; Matsuoka, Risa ; Hanmoto, Taizo ; Ikari, Takahiro ; Endo, Masato ; Omori, Katsunori ; Nakano, Masaki ; Yashima, Sayaka ; Ejiri, Sadakazu ; Taya, Toshiki ; Nakashima, Hiroshi ; Shimizu, Nobuaki ; Nakamura, Masahisa ; Kondo, Takashi ; Hayakawa, Kazuichi ; Takasaki, Ichiro ; Kaminishi, Atsushi ; Akatsuka, Ryosuke ; Sasayama, Yuichi ; Nishiuchi, Takumi ; Nara, Masayuki ; Iseki, Hachiro ; Chowdhury, Vishwajit S. ; Wada, Shigehito ; Ijiri, Kenichi ; Takeuchi, Toshio ; Suzuki, Tohru ; Ando, Hironori ; Matsuda, Kouhei ; Somei, Masanori ; Mishima, Hiroyuki ; Mikuni-Takagaki, Yuko ; Funahashi, Hisayuki ; Takahashi, Akihisa ; Watanabe, Yoshinari ; Maeda, Masahiro ; Uchida, Hideaki ; Hayashi, Akio ; Kambegawa, Akira ; Seki, Azusa ; Yano, Sachiko ; Shimazu, Toru ; Suzuki, Hiromi ; Hirayama, Jun ; Suzuki, Nobuo. / Melatonin is a potential drug for the prevention of bone loss during space flight. In: Journal of Pineal Research. 2019 ; Vol. 67, No. 3.
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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 κB 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.",
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