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Cited by 89Spaceflight effects on biologyBone Metabolism and DiseasesCircadian rhythm and melatonin

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

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Ikegame, Mika, Hattori, Atsuhiko, Tabata, Makoto J., Kitamura, Kei‐ichiro, Tabuchi, Yoshiaki, Furusawa, Yukihiro, Maruyama, Yusuke, Yamamoto, Tatsuki +45 more·2019·Journal of Pineal Research
DOI 10.1111/jpi.12594PMC PMC6771646
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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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  • Melatonin stimulated calcitonin mRNA expression and decreased RANKL mRNA expression in cultured fish scales during an 11-day space flight.

    “melatonin, a well-tolerated and widely available compound, stimulated calcitonin mRNA expression and decreased RANKL mRNA expression in cultured fish scales (a surrogate for bone cultures) during an 11-day space flight”

    From Osteoclasts and Microgravity (2020) · cites this paper as [78]

    The Results section on bone-related gene expression reports that melatonin increased Calcitonin mRNA and suppressed the microgravity-associated increase in Rankl mRNA in regenerating goldfish scales. The Methods section on the space-flight experiment says the scales were incubated in flight for 86 hours, not 11 days; our copy does not substantiate the claimed duration for these measurements. (LLM, conf=0.86)

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Cited by

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Authors
Ikegame, M., Hattori, A., Tabata, M. J., Kitamura, K., 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, V. S., 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.
Affiliations
  • Okayama University (JP)
  • Tokyo Medical and Dental University (JP)
  • Kanazawa University (JP)
  • University of Toyama (JP)
  • Tokyo University of Marine Science and Technology (JP)
  • Asia University (JP)
  • Asahi University (JP)
  • Agilent Technologies (Japan) (JP)
  • Waseda University (JP)
  • Kyushu University (JP)
  • The University of Tokyo (JP)
  • Tohoku University (JP)
  • Sado Island Center for Ecological Sustainability, Niigata University (JP)
  • Tsurumi University (JP)
  • Kanagawa Dental University (JP)
  • Department of Physical Therapy, Faculty of Makuhari Human Care Tohto University Mihama‐ku Japan
  • Gunma University Hospital (JP)
  • Frontier Science and Social Co-creation Initiative, Kanazawa University (JP)
  • Molecular Devices Japan Ltd. Chuo‐ku Japan
  • Kambegawa Laboratory Komae Japan
  • HAMRI Co. Ltd. Koga Japan
  • Japan Aerospace Exploration Agency (JP)
  • Japan Space Forum (JP)
  • Komatsu University (JP)
Corresponding author
Suzuki, Nobuo
ORCID
Venue
Journal of Pineal Research
Publisher
Wiley
Published
2019-07-19
Volume
67
Issue
3
Pages
e12594-e12594
ISSN
  • 0742-3098 (ISSN-L)
  • 1600-079X
DOI
10.1111/jpi.12594
PMC
PMC6771646
OpenAlex
W2960076857
Cited by
89
References
4
Citations by year
2026: 7 · 2025: 12 · 2024: 10 · 2023: 6 · 2022: 14 · 2021: 23 · 2020: 13 · 2019: 3
FWCI
9.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Pineal Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Institute of Nature and Environmental Technology, Kanazawa University
  • Kanazawa University
  • Japan Society for the Promotion of Science (18H02473, 18K06331, 24620004, 18K06312, 18K06432, 17H03867, 18K07668, 20K20309, 18K11016, 16H04812, 16K11442)
  • Japan Aerospace Exploration Agency
Topics
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords
melatonin, bone loss, spaceflight, microgravity, osteoporosis, osteoclasts, osteoclastogenesis, calcitonin, RANKL, bone metabolism, astronauts
MeSH terms
Animals, Bone Resorption, Calcitonin, Cell Differentiation, Goldfish, Immunohistochemistry, Melatonin, Osteoclasts, RNA, Messenger, Space Flight, Weightlessness, Bone Density, NF-kappa B, Rats, Real-Time Polymerase Chain Reaction

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