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Bortezomib prevents ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Bone homeostasis is achieved through coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. When the balance is skewed in favor of osteoclasts due to hormonal or inflammatory issues, pathologic bone loss occurs leading to conditions such as osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is the first in-class of proteasome inhibitors used as an anti-myeloma agent. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor κB ligand (RANKL)—dependent osteoclast differentiation of mouse bone marrow macrophages. Bortezomib significantly reduced the induction of osteoclast marker genes and proteins including nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). The intraperitoneal injection of bortezomib reduced ovariectomy-induced osteoclastogenesis and protected the mice from bone loss. These data propose novel use of bortezomib as a potential anti-resorptive agent.

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Acknowledgements

This work was supported by Grants from the National Research Foundation of Korea (NRF) Grants funded by the Korean government (NRF-2012M3A9B6055415, NRF-2017R1A2B4004618, and NRF-2017R1A5A2015391).

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Author notes

  1. Sung-Hyun Kim, Myoung Ok Kim and Hyo Jeong Kim contributed equally to this work.

Authors and Affiliations

  1. Institute of Life Science and Biotechnology, Kyungpook National University, Daegu, South Korea

    Sung-Hyun Kim

  2. School of Animal BT Sciences, Kyungpook National University, Sangju, South Korea

    Myoung Ok Kim

  3. Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, South Korea

    Hyo Jeong Kim, Sanjiv Neupane, Jae-Young Kim & Youngkyun Lee

  4. Department of Oral Physiology, School of Dentistry & Institute of Translational Dental Science, Pusan National University, Yangsan, 626-810, South Korea

    Hyung Joon Kim

  5. Department of Oral Pathology, School of Dentistry & Institute of Translational Dental Science, Pusan National University, Yangsan, 626-810, South Korea

    Ji Hye Lee

  6. Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul, 110-749, South Korea

    Hong-Hee Kim

  7. Institute for Hard Tissue and Bio-tooth Regeneration (IHBR), School of Dentistry, Kyungpook National University, Daegu, 700-412, South Korea

    Youngkyun Lee

  8. School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, South Korea

    Youngkyun Lee

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  1. Sung-Hyun Kim
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  2. Myoung Ok Kim
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Contributions

S-HK, MOK, and HJK performed the experiments, analyzed the data, and wrote the paper. HJK, JHL, SN, H-HK, and J-YK performed the experiments and analyzed data. YL designed and performed experiments, analyzed data, and wrote the paper.

Corresponding author

Correspondence to Youngkyun Lee.

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The authors declare no conflict of interest.

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Kim, SH., Kim, M.O., Kim, H.J. et al. Bortezomib prevents ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation. J Bone Miner Metab 36, 537–546 (2018). https://doi.org/10.1007/s00774-017-0871-2

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  • DOI: https://doi.org/10.1007/s00774-017-0871-2

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