Abstract
Microgravity causes both muscle and bone loss. Although we previously revealed that gravity change influences muscle and bone through the vestibular system in mice, its detailed mechanism has not been elucidated. In this study, we investigated the roles of olfactomedin 1 (OLFM1), whose expression was upregulated during hypergravity in the soleus muscle, in mouse bone cells. Vestibular lesion significantly blunted OLFM1 expression in the soleus muscle and serum OLFM1 levels enhanced by hypergravity in mice. Moreover, a phosphatidylinositol 3-kinase inhibitor antagonized shear stress-enhanced OLFM1 expression in C2C12 myotubes. As for the effects of OLFM1 on bone cells, OLFM1 inhibited osteoclast formation from mouse bone marrow cells and mouse preosteoclastic RAW264.7 cells. Moreover, OLFM1 suppressed RANKL expression and nuclear factor-κB signaling in mouse osteoblasts. Serum OLFM1 levels were positively related to OLFM1 mRNA levels in the soleus muscle and trabecular bone mineral density of mice. In conclusion, we first showed that OLFM1 suppresses osteoclast formation and RANKL expression in mouse cells.
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The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
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Acknowledgements
This study was partly supported by Grant-in-Aid for Scientific Research (19K07310) to N.K. and (C:18K06850) to H.M. and a Grant-in-Aid for Scientific Research on Innovative Areas (Grant Number 15H05940, “Living in Space”) to H.K. and H.M. from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and a grant (JX-PSPC-454676) to H.M. from the Japan Aerospace Exploration Agency.
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HK contributed to the conception and design of the research. TS, NK, YT, MI and HM performed the experiments. TS and NK analyzed the data. TS, NK and HK interpreted the results of the experiments. TS prepared the figures. TS drafted the manuscript. HK edited and revised the manuscript. All authors approved the final version of the manuscript.
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Takeshi Shimoide, Naoyuki Kawao, Hironobu Morita, Masayoshi Ishida, Yoshimasa Takafuji and Hiroshi Kaji declare that they have no conflicts of interest.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This study does not contain any studies with human participants performed by any of the authors.
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Shimoide, T., Kawao, N., Morita, H. et al. Roles of Olfactomedin 1 in Muscle and Bone Alterations Induced by Gravity Change in Mice. Calcif Tissue Int 107, 180–190 (2020). https://doi.org/10.1007/s00223-020-00710-6
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DOI: https://doi.org/10.1007/s00223-020-00710-6