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Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair.

eLife | 2018

Bone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses in neighboring cells. Osteoblasts contained ATP-rich vesicles that were released upon mechanical stimulation. Surprisingly, interventions that promoted vesicular release reduced ATP release, while inhibitors of vesicular release potentiated ATP release. Searching for an alternative ATP release route, we found that mechanical stresses induced reversible cell membrane injury in vitro and in vivo. Ca2+/PLC/PKC-dependent vesicular exocytosis facilitated membrane repair, thereby minimizing cell injury and reducing ATP release. Priming cellular repair machinery prior to mechanical stimulation reduced subsequent membrane injury and ATP release, linking cellular mechanosensitivity to prior mechanical exposure. Thus, our findings position ATP release as an integrated readout of membrane injury and repair.

Pubmed ID: 30324907 RIS Download

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Associated grants

  • Agency: CIHR, Canada
    Id: MOP-77643
  • Agency: Natural Sciences and Engineering Research Council of Canada, International
    Id: RGPIN-288253

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C2C12 (tool)

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C57BL/6J (tool)

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Phospho-PKC Antibody Sampler Kit (antibody)

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GAPDH (D16H11) XP Rabbit mAb (antibody)

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PKCzeta (C24E6) Rabbit Antibody (antibody)

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PKCα Antibody (antibody)

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SEA/GnJ (organism)

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Mus musculus with name SEA/GnJ from IMSR.

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GAPDH (D16H11) XP Rabbit mAb (antibody)

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PKCdelta (D10E2) Rabbit mAb (antibody)

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SEA/GnJ (organism)

RRID:IMSR_JAX:000644

Mus musculus with name SEA/GnJ from IMSR.

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Anti-rabbit IgG, HRP-linked Antibody (antibody)

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Phospho-PKC Antibody Sampler Kit (antibody)

RRID:AB_330848

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PKCα Antibody (antibody)

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PKCzeta (C24E6) Rabbit Antibody (antibody)

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