Mediation of the Acute Stress Response by the Skeleton
Mediation of the Acute Stress Response by the Skeleton
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DOI：
10.1016/j.cmet.2019.08.012
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发表时间：
2019-11-05
期刊：
影响因子：
29
通讯作者：
Karsenty, Gerard
中科院分区：
文献类型：
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作者：
Berger, Julian Meyer;Singh, Parminder;Karsenty, Gerard
我们假设，骨骼的进化，部分是为了增强多骨脊椎动物在野外躲避危险的能力。为了支持这一观点，我们在这里表明，骨源性信号是必要的发展急性应激反应（ASR）。事实上，在小鼠、大鼠（啮齿动物）和人类中暴露于各种类型的应激源导致循环生物活性骨钙素的快速和选择性激增，因为应激源有利于成骨细胞摄取谷氨酸，这防止了骨钙素在其分泌之前的失活。骨钙素允许ASR的表现通过在突触后副交感神经元中的信号传导来展开以抑制它们的活性，从而使交感神经张力不受对抗。像野生型动物一样，肾上腺切除的啮齿动物和肾上腺不足的患者可以发展为ASR，遗传研究表明这是由于它们的高循环骨钙素水平。我们认为骨钙素是一种骨脊椎动物特异性的ASR内分泌调节因子。
We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and selective surge of circulating bioactive osteocalcin because stressors favor the uptake by osteoblasts of glutamate, which prevents inactivation of osteocalcin prior to its secretion. Osteocalcin permits manifestations of the ASR to unfold by signaling in post-synaptic parasympathetic neurons to inhibit their activity, thereby leaving the sympathetic tone unopposed. Like wild-type animals, adrenalectomized rodents and adrenal-insufficient patients can develop an ASR, and genetic studies suggest that this is due to their high circulating osteocalcin levels. We propose that osteocalcin defines a bony-vertebrate-specific endocrine mediation of the ASR.