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Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

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Abstract

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.

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Acknowledgments

We would like to thank Keisuke Goto for performing the surgeries and kindly making tissue available from patients, as well as Ai Ikeda and Tomoko Kawanami for their technical assistance in the laboratory. This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, the Takeda Science Foundation, and the Mochida Memorial Foundation for Medical and Pharmaceutical Research.

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Authors and Affiliations

  1. Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692, Japan

    Shin-ichiro Hino, Shinichi Kondo, Kazuya Yoshinaga, Atsushi Saito, Tomohiko Murakami, Soshi Kanemoto, Hiroshi Sekiya, Kazuyasu Chihara, Yuji Aikawa & Kazunori Imaizumi

  2. Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu, 502-8585, Japan

    Hideaki Hara

  3. Department of Clinical Neuroscience, Psychiatry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Takashi Kudo

  4. Department of Orthopaedic Surgery, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki, 889-1692, Japan

    Tomohisa Sekimoto, Taro Funamoto & Etsuo Chosa

Authors
  1. Shin-ichiro Hino
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  2. Shinichi Kondo
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  3. Kazuya Yoshinaga
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  4. Atsushi Saito
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  5. Tomohiko Murakami
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  7. Hiroshi Sekiya
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  8. Kazuyasu Chihara
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  9. Yuji Aikawa
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  10. Hideaki Hara
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  11. Takashi Kudo
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  12. Tomohisa Sekimoto
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  13. Taro Funamoto
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  14. Etsuo Chosa
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  15. Kazunori Imaizumi
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Corresponding author

Correspondence to Kazunori Imaizumi.

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Hino, Si., Kondo, S., Yoshinaga, K. et al. Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis. J Bone Miner Metab 28, 131–138 (2010). https://doi.org/10.1007/s00774-009-0117-z

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  • DOI: https://doi.org/10.1007/s00774-009-0117-z

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