Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
Shriners Hospital for Children - Canada, Montreal, Quebec, Canada.
Elife. 2018 Oct 16;7:e37812. doi: 10.7554/eLife.37812.
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 and . Ca/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.
骨细胞感知并积极适应物理干扰，以防止发生临界损伤。三磷酸腺苷（ATP）的释放是细胞对机械刺激的最早反应之一。对单个鼠成骨细胞进行机械刺激，导致释放 70 ± 24 毫微微摩尔的 ATP，从而刺激邻近细胞的钙反应。成骨细胞内含有富含 ATP 的囊泡，这些囊泡在受到机械刺激时会被释放。令人惊讶的是，促进囊泡释放的干预措施会减少 ATP 的释放，而抑制囊泡释放的措施则会增强 ATP 的释放。在寻找替代的 ATP 释放途径时，我们发现机械应力会诱导细胞膜可逆性损伤 和. Ca/PLC/PKC 依赖性囊泡胞吐作用有助于膜修复，从而最大限度地减少细胞损伤并减少 ATP 释放。在进行机械刺激之前激活细胞修复机制，可减少随后的膜损伤和 ATP 释放，将细胞的机械敏感性与先前的机械暴露联系起来。因此，我们的发现将 ATP 释放定位为膜损伤和修复的综合指标。
