Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction

Tina Kringelbach, Derya Aslan, Ivana Novak, M. Ellegaard, Susanne Syberg, Christina Andersen, Kim Kristiansen, Ole Vang, Peter Schwarz, Niklas Jørgensen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction.
    OriginalsprogDansk
    TidsskriftCellular Signalling
    Vol/bind27
    Udgave nummer12
    Sider (fra-til)2401-2409
    ISSN0898-6568
    DOI
    StatusUdgivet - 2015

    Citer dette

    Kringelbach, T., Aslan, D., Novak, I., Ellegaard, M., Syberg, S., Andersen, C., ... Jørgensen, N. (2015). Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction. Cellular Signalling, 27(12), 2401-2409. https://doi.org/10.1016/j.cellsig.2015.08.016
    Kringelbach, Tina ; Aslan, Derya ; Novak, Ivana ; Ellegaard, M. ; Syberg, Susanne ; Andersen, Christina ; Kristiansen, Kim ; Vang, Ole ; Schwarz, Peter ; Jørgensen, Niklas . / Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction. I: Cellular Signalling. 2015 ; Bind 27, Nr. 12. s. 2401-2409.
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    title = "Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction",
    abstract = "Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction.",
    author = "Tina Kringelbach and Derya Aslan and Ivana Novak and M. Ellegaard and Susanne Syberg and Christina Andersen and Kim Kristiansen and Ole Vang and Peter Schwarz and Niklas J{\o}rgensen",
    year = "2015",
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    language = "Dansk",
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    Kringelbach, T, Aslan, D, Novak, I, Ellegaard, M, Syberg, S, Andersen, C, Kristiansen, K, Vang, O, Schwarz, P & Jørgensen, N 2015, 'Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction', Cellular Signalling, bind 27, nr. 12, s. 2401-2409. https://doi.org/10.1016/j.cellsig.2015.08.016

    Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction. / Kringelbach, Tina ; Aslan, Derya; Novak, Ivana; Ellegaard, M.; Syberg, Susanne; Andersen, Christina ; Kristiansen, Kim ; Vang, Ole; Schwarz, Peter; Jørgensen, Niklas .

    I: Cellular Signalling, Bind 27, Nr. 12, 2015, s. 2401-2409.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction

    AU - Kringelbach, Tina

    AU - Aslan, Derya

    AU - Novak, Ivana

    AU - Ellegaard, M.

    AU - Syberg, Susanne

    AU - Andersen, Christina

    AU - Kristiansen, Kim

    AU - Vang, Ole

    AU - Schwarz, Peter

    AU - Jørgensen, Niklas

    PY - 2015

    Y1 - 2015

    N2 - Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction.

    AB - Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction.

    U2 - 10.1016/j.cellsig.2015.08.016

    DO - 10.1016/j.cellsig.2015.08.016

    M3 - Tidsskriftartikel

    VL - 27

    SP - 2401

    EP - 2409

    JO - Cellular Signalling

    JF - Cellular Signalling

    SN - 0898-6568

    IS - 12

    ER -

    Kringelbach T, Aslan D, Novak I, Ellegaard M, Syberg S, Andersen C et al. Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction. Cellular Signalling. 2015;27(12):2401-2409. https://doi.org/10.1016/j.cellsig.2015.08.016