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Psychosine inhibits osteoclastogenesis and bone resorption via G protein-coupled receptor 65

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Abstract

Background

It was recently reported that G protein-coupled receptor 65 (GPR65) suppresses ovariectomy-induced bone loss.

Aim

The present study investigated the role of the lysosphingolipid psychosine, a GPR65 ligand, on osteoclastic differentiation and bone resorption.

Methods

Osteoclasts were differentiated from mouse bone marrow macrophages. Tartrate-resistant acid phosphatase-positive multinucleated cells were considered to be osteoclasts, and the resorption area was measured by incubating the cells on dentine discs. The expression levels of osteoclast differentiation markers were assessed by qRT-PCR. GPR65 siRNA and its scrambled siRNA were transfected with lipofectamine. Intracellular cyclic adenosine monophosphate (cAMP) levels were assessed using a direct enzyme immunoassay.

Results

Psychosine inhibited osteoclastogenesis and in vitro bone resorption without any significant effect on the viability of pre-osteoclasts, decreased the expression of osteoclast differentiation markers significantly, and increased intracellular cAMP levels. The knockdown of GPR65 by its siRNA restored osteoclastogenesis and decreased cAMP levels in the presence of psychosine.

Conclusion

Psychosine inhibits osteoclastogenesis by increasing intracellular cAMP levels via GPR65.

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Acknowledgments

This study was supported by a grant from the Korea Health Technology R&D project, Ministry of Health and Welfare, Republic of Korea (project No.: HI14C2185) and by a grant from the Asan Institute for Life Sciences, Seoul, Republic of Korea (project No.: 2014-586).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. All procedures performed in studies involving animals were approved by the Institutional Animal Care and Use Committee of the Asan Institute for Life Sciences (Seoul, Korea).

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    Authors and Affiliations

    1. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-2Dong, Songpa-Gu, Seoul, 138-736, South Korea

      S. H. Ahn, H. Kim, B.-J. Kim, S. H. Lee & J.-M. Koh

    2. Asan Institute for Life Sciences, Seoul, 138-736, South Korea

      S.-Y. Lee, J.-E. Baek, S.-Y. Lee, S.-Y. Park & Y.-S. Lee

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    1. S. H. Ahn
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    Correspondence to B.-J. Kim.

    Additional information

    S. H. Ahn and S.-Y. Lee contributed equally to this work.

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    Ahn, S.H., Lee, SY., Baek, JE. et al. Psychosine inhibits osteoclastogenesis and bone resorption via G protein-coupled receptor 65. J Endocrinol Invest 38, 891–899 (2015). https://doi.org/10.1007/s40618-015-0276-9

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    • DOI: https://doi.org/10.1007/s40618-015-0276-9

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