Cited by 484Bone Metabolism and DiseasesNeurogenesis and neuroplasticity mechanismsBone health and osteoporosis research

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Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions

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Oury, Franck, Khrimian, Lori, Denny, Christine A., Gardin, Antoine, Chamouni, Alexandre, Goeden, Nick, Huang, Yung-yu, Lee, Hojoon, Srinivas, Prashanth, Gao, Xiao-Bing, Suyama, Shigetomo, Langer, Thomas, Mann, John. J., Horvath, Tamas L., Bonnin, Alexandre, Karsenty, Gerard·2013·Cell

DOI 10.1016/j.cell.2013.08.042PMC PMC3864001

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Abstract

The powerful regulation of bone mass exerted by the brain suggests the existence of bone-derived signals modulating this regulation or other functions of the brain. We show here that the osteoblast-derived hormone osteocalcin crosses the blood-brain barrier, binds to neurons of the brainstem, midbrain, and hippocampus, enhances the synthesis of monoamine neurotransmitters, inhibits GABA synthesis, prevents anxiety and depression, and favors learning and memory independently of its metabolic functions. In addition to these postnatal functions, maternal osteocalcin crosses the placenta during pregnancy and prevents neuronal apoptosis before embryos synthesize this hormone. As a result, the severity of the neuroanatomical defects and learning and memory deficits of Osteocalcin(-/-) mice is determined by the maternal genotype, and delivering osteocalcin to pregnant Osteocalcin(-/-) mothers rescues these abnormalities in their Osteocalcin(-/-) progeny. This study reveals that the skeleton via osteocalcin influences cognition and contributes to the maternal influence on fetal brain development.

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Su, X., Mao, Y., Yang, C., Liao, H., Zhao, H., Zhang, Y., Wei, W., Bi, S., Liu, B., Fu, X., et al. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1974960
Advances in Bone-Brain Axis Research: Bidirectional Regulatory Mechanisms and Evidentiary Boundaries
熊, 昭. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.16103506
Preconditioning with Menaquinone-7 and Environmental Enrichment Produces Distinct Osteocalcin and Neuroplasticity Responses Following Chronic Social Defeat Stress
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Authors: Oury, F., Khrimian, L., Denny, C. A., Gardin, A., Chamouni, A., Goeden, N., Huang, Y.-Y., Lee, H., Srinivas, P., Gao, X.-B., Suyama, S., Langer, T., Mann, J. J., Horvath, T. L., Bonnin, A., & Karsenty, G.
Affiliations: Columbia University (US)
University of Southern California (US)
New York State Psychiatric Institute (US)
Yale University (US)
Sanofi (Germany) (DE)
ORCID: Oury, Franck
Khrimian, Lori
Denny, Christine A.
Gardin, Antoine
Lee, Hojoon
Gao, Xiao-Bing
Langer, Thomas
Bonnin, Alexandre
Venue: Cell
Publisher: Elsevier BV
Published: 2013-09
Volume: 155
Issue: 1
Pages: 228-241
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2013.08.042
PMC: PMC3864001
OpenAlex: W2017975043
Cited by: 484
References: 58
Citations by year: 2026: 33 · 2025: 43 · 2024: 40 · 2023: 39 · 2022: 40 · 2021: 45 · 2020: 77 · 2019: 35 · 2018: 31 · 2017: 25 · 2016: 27 · 2015: 17 · 2014: 28 · 2013: 4
FWCI: 11.34
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 390 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Sanofi
National Institutes of Health
National Institute on Aging (P01AG032959)
National Institute of General Medical Sciences (T32GM007088)
National Institute of Diabetes and Digestive and Kidney Diseases (DP1DK098058)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR045548)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: osteocalcin, blood-brain barrier, GABA synthesis, anxiety, depression, learning and memory, neuronal apoptosis, placental transfer, maternal genotype, fetal brain development
MeSH terms: Aging, Animals, Brain, Female, Fetus, Pregnancy, Signal Transduction, Osteocalcin, Neurotransmitter Agents, Mice

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Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions

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