ArticleCell metabolism2019
Mediation of the Acute Stress Response by the Skeleton.
Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
96 citing papers in PubMed, 163 citations in OpenAlex.
- Stress, needs, and behaviour: understanding chronic stress in pet domestic dogs (Canis lupus familiaris) from the prism of needs.Biological reviews of the Cambridge Philosophical Society · 2026Review
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Osteocalcin Beyond Bone: Molecular Mechanisms, Endocrine Networks, and Translational Perspectives Across Metabolism, Neurobiology, and Chronic Disease.International journal of molecular sciences · 2026Review
- Functional nucleic acid Hydrogels: Paving the way for Next-generation bone and cartilage regeneration.Materials today. Bio · 2026Review
- PTH induced osteoblast Slit3 to decrease aberrant sensory innervation in degenerated vertebral endplates to relieve low back pain in mice.Bone research · 2026Article
- Two decades into the crosstalk between bone and energy metabolism.Nature reviews. Endocrinology · 2025Article
- Brain-Bone Axis in Physiological and Pathological Conditions.International journal of molecular sciences · 2025Review
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- Cannabidiol Lipid Nanoparticles Stabilize Gut-Brain-Bone Axis Integrity and Enhance Neuroplasticity in Stressed Rats: A Comparison with Atomoxetine and Escitalopram.International journal of molecular sciences · 2025Article
- Short-Term Effects of Visceral Manual Therapy on Autonomic Nervous System Modulation in Individuals with Clinically Based Bruxism: A Randomized Controlled Trial.Dentistry journal · 2025Article
- Article
- Bone mechanical loading reduces heart rate and increases heart rate variability in mice.Bone reports · 2025Article
- MLO-Y4 fluid flow shear stress conditioned media enhances cardiac contractility and intracellular CaAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Strategies for promoting neurovascularization in bone regeneration.Military Medical Research · 2025Review
- Osteocalcin and GPR158: linking bone and brain function.Frontiers in cell and developmental biology · 2025Review
- Osteocalcin in human breast milk over the course of lactation.Frontiers in endocrinology · 2025Observational
- Association of baseline osteocalcin and femoral neck bone mineral density in healthy women with future risk of fractures, cardiovascular disease, diabetes and death.Frontiers in endocrinology · 2025Article
- Sinomenine in cerebral ischemia: mechanisms, delivery strategies, and the emerging multifunctional biomaterials of the bone-brain axis.Frontiers in medicine · 2025Review
- The role of osteocalcin in regulating the acute stress response.Frontiers in pharmacology · 2025Review
- Editorial: Bone-organ axis: an expanding universe.Frontiers in endocrinology · 2025Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.