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Effects of the bisphosphonate risedronate on osteopenia in OASIS-deficient mice

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Abstract

Endoplasmic reticulum (ER) stress has been reported to be linked to various diseases such as diabetes, neurodegenerative diseases, and osteogenesis imperfecta (OI). Old astrocyte specifically induced substance (OASIS), a novel type of ER stress transducer, is a basic leucine zipper transcription factor belonging to the CREB/ATF family and is markedly expressed in osteoblasts. Recently, we demonstrated that OASIS activates the transcription of the gene for type I collagen, Col1a1, and contributes to the secretion of bone matrix proteins in osteoblasts. OASIS−/− mice exhibit severe osteopenia involving a decrease in type I collagen in the bone matrix and a dysfunction of osteoblasts, which show abnormal expansion of the rough ER. These phenotypic features of osteopenia are similar to those observed in OI type I. In this study, we investigated whether administration of the third-generation bisphosphonate risedronate (RIS) is effective for treating osteopenia in OASIS−/− mice. Histological and histomorphometric analyses revealed that the trabecular bones increased dramatically in OASIS−/− mice treated with RIS, owing to the inhibition of bone resorption. Intriguingly, the abnormal expansion of the rough ER in OASIS−/− osteoblasts was improved by the treatment with RIS. Taken together, we conclude that OASIS−/− mice will be useful as new model mice for evaluating the medicinal effects of osteopenia treatments and developing new drugs for the osteopenia associated with diseases such as OI and osteoporosis.

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Acknowledgments

We thank Ms. Tomoko Kawanami and Ms. Ikuyo Tuchimoti for technical support. This work was supported by grants from the Japan Society for the Promotion of Science KAKENHI (nos. 20059028, 20890175, 21790323, 21790174, and 20-3757), the Naito Foundation, the Sumitomo Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and Astellas Foundation for Research on Metabolic Disorders.

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Authors and Affiliations

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

    Hiroshi Sekiya, Tomohiko Murakami, Atsushi Saito, Shin-ichiro Hino, Kenji Tsumagari, Kimiko Ochiai & Kazunori Imaizumi

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  1. Hiroshi Sekiya
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  2. Tomohiko Murakami
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  7. Kazunori Imaizumi
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Correspondence to Tomohiko Murakami or Kazunori Imaizumi.

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Sekiya, H., Murakami, T., Saito, A. et al. Effects of the bisphosphonate risedronate on osteopenia in OASIS-deficient mice. J Bone Miner Metab 28, 384–394 (2010). https://doi.org/10.1007/s00774-009-0142-y

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  • DOI: https://doi.org/10.1007/s00774-009-0142-y

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