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

Mika Ikegame(Okayama University), Atsuhiko Hattori(Tokyo Medical and Dental University), M. Tabata(Tokyo Medical and Dental University), Kei‐ichiro Kitamura(Kanazawa University), Yoshiaki Tabuchi(University of Toyama), Yukihiro Furusawa(Toyama Prefectural University), Yusuke Maruyama(Tokyo Medical and Dental University), Tatsuki Yamamoto(Kanazawa University), Toshio Sekiguchi(Kanazawa University), Risa Matsuoka(Tokyo Medical and Dental University), Taizo Hanmoto(Kanazawa University), Takahiro Ikari(Kanazawa University), Masato Endo(Tokyo University of Marine Science and Technology), Katsunori Omori(Asia University), Masaki Nakano(Tokyo Medical and Dental University), Sayaka Yashima(Tokyo Medical and Dental University), Sadakazu Ejiri(Asahi University), Toshiki Taya(Agilent Technologies (Japan)), Hiroshi Nakashima(Kanazawa University), Nobuaki Shimizu(Kanazawa University), Masahisa Nakamura(Waseda University), Takashi Kondo(University of Toyama), Kazuichi Hayakawa(Kanazawa University), Ichiro Takasaki(University of Toyama), Atsushi Kaminishi(Kanazawa University), R Akatsuka(Tokyo Medical and Dental University), Yuichi Sasayama(Kanazawa University), Takumi Nishiuchi(Kanazawa University), Masayuki Nara(Tokyo Medical and Dental University), Hachiro Iseki(Tokyo Medical and Dental University), Vishwajit S. Chowdhury(Kyushu University), Shigehito Wada(University of Toyama), Kenichi Ijiri(Japan Radioisotope Association), Toshio Takeuchi(Tokyo University of Marine Science and Technology), Tohru Suzuki(Tohoku University), Hironori Ando(Sado General Hospital), Kouhei Matsuda(University of Toyama), Masanori Somei(Kanazawa University), Hiroyuki Mishima(Tsurumi University), Yuko Mikuni‐Takagaki(Kanagawa Dental University), Hisayuki Funahashi(Seisa Dohto University), Akihisa Takahashi(Gunma University Hospital), Yoshinari Watanabe(Kanazawa University), Masahiro Maeda(Molecular Devices (United Kingdom)), Hideaki Uchida(Agilent Technologies (Japan)), Akio Hayashi(Agilent Technologies (Japan)), Akira Kambegawa(Komatsu (Japan)), Azusa Seki(Hamari Chemicals (Japan)), Sachiko Yano(Japan Aerospace Exploration Agency), Toru Shimazu(Japan Space Forum), Hiromi Suzuki(Japan Space Forum), Jun Hirayama(Komatsu University), Nobuo Suzuki(Kanazawa University)
Journal of Pineal Research
July 9, 2019
Cited by 87Open Access
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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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