
Cell Metabolism| VOLUME 30, ISSUE 5, P890-902.E8, NOVEMBER 05, 2019
- Julian Meyer Berger
- Parminder Singh
- Lori Khrimian
- Kamal Rahmouni
- Xiao-Bing Gao
- Gerard Karsenty 9
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Published:September 12, 2019
DOI:https://doi.org/10.1016/j.cmet.2019.08.012PlumX Metrics
Highlights
- The ASR stimulates osteocalcin release from bone within minutes
- Glutamate uptake into osteoblasts is required for osteocalcin release during an ASR
- Osteocalcin inhibits the parasympathetic tone during an ASR
- In adrenal insufficiency, increased osteocalcin levels enable an ASR to occur
Summary
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.