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αVβ3 Integrin ligands enhance volume-sensitive calcium influx in mechanically stretched osteocytes

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Abstract

We propose that specific osteocyte–matrix interactions regulate the volume-sensitive calcium influx pathway, which we have shown is mediated by stretch-activated cation channels (SA-Cat) and is essential for the stretch-activated anabolic response in bone. The current study measured the hypotonic swelling-induced increase in cytosolic calcium concentration, [Ca2+]i, in rat osteocytes, and found that cells adherent to different matrices behave differently. Osteopontin and vitronectin, matrix molecules that bind the αVβ3 integrin, induced larger responses to the hypotonic swelling than other matrix molecules that bind other integrins. Addition of echistatin, which is a soluble αVβ3 ligand, significantly enhanced the hypotonic [Ca2+]i increase in addition to inducing an immediate increase in [Ca2+]i by itself. These results strongly support the contention that αVβ3 integrin signaling in osteocytes interacts with that in mechanotransduction, which is downstream of SA-Cat.

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Authors and Affiliations

  1. National Hyogo Chuo Hospital, 1314 Ohara, Sanda, Hyogo, 669-1515, Japan

    Akimitsu Miyauchi, Yasuyuki Takagi, Yoshio Yoshimoto & Hitoshi Ishikawa

  2. Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Osaka, Japan

    Masayuki Gotoh & Kohei Notoya

  3. Department of Orthodontics and Dentofacial Orthopedics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

    Hiroshi Kamioka & Teruko Takano-Yamamoto

  4. Department of Oral Surgery, Toho University, Omori Medical Center, Tokyo, Japan

    Hideki Sekiya

  5. Division of Endocrinology and Metabolism, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Kazuo Chihara

  6. Calcium Research Institute, Kishiwada, Japan

    Akimitsu Miyauchi & Takuo Fujita

  7. Department of Functional Biology, Kanagawa Dental College, Yokosuka, Japan

    Yuko Mikuni-Takagaki

Authors
  1. Akimitsu Miyauchi
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  2. Masayuki Gotoh
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  3. Hiroshi Kamioka
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  8. Hitoshi Ishikawa
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  9. Kazuo Chihara
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  10. Teruko Takano-Yamamoto
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  12. Yuko Mikuni-Takagaki
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Corresponding author

Correspondence to Akimitsu Miyauchi.

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Miyauchi, A., Gotoh, M., Kamioka, H. et al. αVβ3 Integrin ligands enhance volume-sensitive calcium influx in mechanically stretched osteocytes. J Bone Miner Metab 24, 498–504 (2006). https://doi.org/10.1007/s00774-006-0716-x

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  • DOI: https://doi.org/10.1007/s00774-006-0716-x

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