The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Osteocalcin also stimulates the synthesis of monoamine neurotransmitters in the hippocampus and inhibits gamma-aminobutyric acid (GABA) synthesis, improving learning and memory skills [207].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [207]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Place navigation impaired in rats with hippocampal lesions
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O'Keefe, J. (1982) · Nature · doi:10.1038/297681a0 · Cited by 6,340
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Self-citationThe tail suspension test: A new method for screening antidepressants in mice
Steru, L., Chermat, R., Thierry, B., & Simon, P. (1985) · Psychopharmacology · doi:10.1007/bf00428203 · Cited by 3,534
Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis
Hales, C. N., & Barker, D. J. P. (1992) · Diabetologia · doi:10.1007/bf00400248 · Cited by 3,294
A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data
Ennaceur, A., & Delacour, J. (1988) · Behavioural Brain Research · doi:10.1016/0166-4328(88)90157-x · Cited by 3,223
Endocrine regulation of energy metabolism by the skeleton
Lee, N. K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J. D., Confavreux, C., Dacquin, R., Mee, P. J., McKee, M. D., Jung, D. Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.047 · Cited by 2,554
Self-citationLeptin Inhibits Bone Formation through a Hypothalamic Relay
Ducy, P., Amling, M., Takeda, S., Priemel, M., Schilling, A. F., Beil, F. T., Shen, J., Vinson, C., Rueger, J. M., & Karsenty, G. (2000) · Cell · doi:10.1016/s0092-8674(00)81558-5 · Cited by 2,077
Self-citationLeptin Regulates Bone Formation via the Sympathetic Nervous System
Takeda, S., Elefteriou, F., Levasseur, R., Liu, X., Zhao, L., Parker, K. L., Armstrong, D., Ducy, P., & Karsenty, G. (2002) · Cell · doi:10.1016/s0092-8674(02)01049-8 · Cited by 1,735
Self-citationIncreased bone formation in osteocalcin-deficient mice
Ducy, P. F., Morris, C., Boyce, B. F., Pinero, G. J., Story, B. M., Dunstan, C. R., Smith, E. A., Bonadio, J. F., Goldstein, S. A., Gundberg, C. M., et al. (1996) · Nature · doi:10.1038/382448a0 · Cited by 1,724
Self-citationCryan, J. F., Mombereau, C., & Vassout, A. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.009 · Cited by 1,674
Synthesis of Serotonin by a Second Tryptophan Hydroxylase Isoform
Walther, D. J., Peter, J., Bashammakh, S., Hörtnagl, H., Voits, M., Fink, H., & Bäder, M. (2003) · Science · doi:10.1126/science.1078197 · Cited by 1,576
Mutations Involving the Transcription Factor CBFA1 Cause Cleidocranial Dysplasia
Mundlos, S., Otto, F., Mundlos, C., Mulliken, J. B., Aylsworth, A. S., Albright, S. G., Lindhout, D., Cole, W. G., Henn, W., Knoll, J. H. M., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80260-3 · Cited by 1,502
David, D. J., Samuels, B. A., Rainer, Q., Wang, J.-W., Marsteller, D., Mendez, I., Drew, M., Craig, D. A., Guiard, B. P., Guilloux, J.-P., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.04.017 · Cited by 1,267
Leptin enters the brain by a saturable system independent of insulin
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., & Maness, L. M. (1996) · Peptides · doi:10.1016/0196-9781(96)00025-3 · Cited by 1,222
Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism
Ferron, M., Wei, J., Yoshizawa, T., Del Fattore, A., DePinho, R. A., Teti, A., Ducy, P., & Karsenty, G. (2010) · Cell · doi:10.1016/j.cell.2010.06.003 · Cited by 1,123
Self-citationVan den Bergh, B. R. H., Mulder, E. J. H., Mennes, M., & Glover, V. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.10.007 · Cited by 1,104
The long-term behavioural consequences of prenatal stress
Weinstock, M. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.03.002 · Cited by 1,098
Tyrosine hydroxylase and regulation of dopamine synthesis
Daubner, S. C., Le, T., & Wang, S. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.12.017 · Cited by 1,092
Exploratory behavior models of anxiety in mice
Crawley, J. N. (1985) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(85)90030-2 · Cited by 756
Yadav, V. K., Oury, F., Suda, N., Liu, Z.-W., Gao, X.-B., Confavreux, C., Klemenhagen, K. C., Tanaka, K. F., Gingrich, J. A., Guo, X. E., et al. (2009) · Cell · doi:10.1016/j.cell.2009.06.051 · Cited by 661
Self-citationCedarbaum, J. M., & Aghajanian, G. K. (1976) · Brain Research · doi:10.1016/0006-8993(76)90297-3 · Cited by 636
Endocrine Regulation of Male Fertility by the Skeleton
Oury, F., Sumara, G., Sumara, O., Ferron, M., Chang, H., Smith, C. E., Hermo, L., Suarez, S., Roth, B. L., Ducy, P., et al. (2011) · Cell · doi:10.1016/j.cell.2011.02.004 · Cited by 628
Self-citationLee, B., Thirunavukkarasu, K., Zhou, L., Pastore, L., Baldini, A., Hecht, J. T., Geoffrey, V., Ducy, P. F., & Karsenty, G. (1997) · Nature Genetics · doi:10.1038/ng0797-307 · Cited by 567
Self-citationJansson, T., & Powell, T. L. (2007) · Clinical Science · doi:10.1042/cs20060339 · Cited by 542
The contribution of bone to whole-organism physiology
Karsenty, G., & Ferron, M. (2012) · Nature · doi:10.1038/nature10763 · Cited by 537
Self-citationLiu, R.-J., van den Pol, A. N., & Aghajanian, G. K. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09453.2002 · Cited by 392
Lira, A., Zhou, M., Castanon, N., Ansorge, M. S., Gordon, J. A., Francis, J. H., Bradley-Moore, M., Lira, J., Underwood, M. D., Arango, V., et al. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00696-6 · Cited by 385
Nagamatsu, L. S. (2012) · Archives of Internal Medicine · doi:10.1001/archinternmed.2012.379 · Cited by 385
Palmiter, R. D. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1417.003 · Cited by 375
Context Fear Learning in the Absence of the Hippocampus
Wiltgen, B. J., Sanders, M. J., Anagnostaras, S., Sage, J. R., & Fanselow, M. S. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2685-05.2006 · Cited by 349
Serum leptin level is a regulator of bone mass
Elefteriou, F., Takeda, S., Ebihara, K., Magré, J., Patano, N., Kim, C. A., Ogawa, Y., Liu, X., Ware, S. M., Craigen, W. J., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308744101 · Cited by 335
Self-citationOsteocalcin regulates murine and human fertility through a pancreas-bone-testis axis
Oury, F., Ferron, M., Huizhen, W., Confavreux, C. B., Xu, L., Lacombe, J., Srinivas, P., Chamouni, A., Lugani, F., Lejeune, H., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65952 · Cited by 276
Self-citationMayorga, A. J., Dalvi, A., Page, M. E., Zimov-Levinson, S., Hen, R., & Lucki, I. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29479-9 · Cited by 209
Denny, C. A., Burghardt, N. S., Schachter, D., Hen, R., & Drew, M. R. (2011) · Hippocampus · doi:10.1002/hipo.20964 · Cited by 208
Self-citationGardier, A. M., Malagié, I., Trillat, A., Jacquot, C., & Artigas, F. (1996) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.1996.tb00145.x · Cited by 198
Maternal adiposity—a determinant of perinatal and offspring outcomes?
Lawlor, D. A., Relton, C., Sattar, N., & Nelson, S. M. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.176 · Cited by 192
Drew, M. R., Denny, C. A., & Hen, R. (2010) · Behavioral Neuroscience · doi:10.1037/a0020081 · Cited by 159
Self-citationGuntur, A. R., & Rosen, C. J. (2012) · Endocrine Practice · doi:10.4158/ep12141.ra · Cited by 150
Behavioral profile of wild mice in the elevated plus-maze test for anxiety
Holmes, A., Parmigiani, S., Ferrari, P. F., Palanza, P., & Rodgers, R. J. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(00)00373-5 · Cited by 148
Hsu, C. L., Nagamatsu, L. S., Davis, J. C., & Liu-Ambrose, T. Y. L. (2012) · Osteoporosis International · doi:10.1007/s00198-012-1992-z · Cited by 136
Tanaka, D. H., Maekawa, K., Yanagawa, Y., Obata, K., & Murakami, F. (2006) · Development · doi:10.1242/dev.02382 · Cited by 134
Oury, F., Yadav, V. K., Wang, Y., Zhou, B., Liu, X. S., Guo, X.-D. E., Tecott, L. H., Schütz, G., Means, A. R., & Karsenty, G. (2010) · Genes & Development · doi:10.1101/gad.1977210 · Cited by 122
Self-citationRao, Y., Liu, Z.-W., Borók, E., Rabenstein, R. L., Shanabrough, M., Lu, M., Picciotto, M. R., Horváth, T. L., & Gao, X. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32829 · Cited by 121
Self-citationPlacental protection of the fetal brain during short-term food deprivation
Broad, K. D., & Keverne, E. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106022108 · Cited by 111
Multiligand Specificity and Wide Tissue Expression of GPRC6A Reveals New Endocrine Networks
Pi, M., & Quarles, L. D. (2012) · Endocrinology · doi:10.1210/en.2011-2117 · Cited by 95
Transgenic Mice Expressing a Ligand-Inducible Cre Recombinase in Osteoblasts and Odontoblasts
Kim, J., Nakashima, K., & Crombrugghe, B. D. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63240-3 · Cited by 94
Leptin Inhibits Bone Formation Not Only in Rodents, but Also in Sheep
Pogoda, P., Egermann, M., Schnell, J. C., Priemel, M., Schilling, A. F., Alini, M., Schinke, T., Rueger, J. M., Schneider, E. H., Clarke, I. J., et al. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060709 · Cited by 88
Method for serum-free culture of late fetal and early postnatal rat brainstem neurons
Kivell, B. M., McDonald, F. J., & Miller, J. H. (2001) · Brain Research Protocols · doi:10.1016/s1385-299x(00)00037-4 · Cited by 64
Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function
Gobbi, G., Cassano, T., Radja, F., Morgese, M. G., Cuomo, V., SANTARELLI, L., Hen, R., & Blier, P. (2006) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2006.07.004 · Cited by 62
Nutrition and molecular markers of bone remodelling
Seibel, M. J. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00011 · Cited by 49
Goeden, N., & Bonnin, A. (2012) · Nature Protocols · doi:10.1038/nprot.2012.144 · Cited by 44
Self-citationCreation and Preliminary Characterization of a Leptin Knockout Rat
Vaira, S., Yang, C., McCoy, A., Keys, K., Xue, S., Weinstein, E. J., Novack, D. V., & Cui, X. (2012) · Endocrinology · doi:10.1210/en.2012-1462 · Cited by 37
The effect of body temperature on the murine electroretinogram
Kong, J., & Gouras, P. (2003) · Documenta Ophthalmologica · doi:10.1023/a:1022988332578 · Cited by 34
Mutational dysostosis (cleidocranial dysostosis).
Soule, A. B. (1946) · PubMed · Cited by 34
Neuronal tryptophan hydroxylase expression in BALB/cJ and C57Bl/6J mice
Bach, H., Arango, V., Huang, Y., Leong, S., Mann, J. J., & Underwood, M. D. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07379.x · Cited by 24
Self-citationMcBrien, H., Turk, J., & Letch, N. (2006) · Clinical Child Psychology and Psychiatry · doi:10.1177/1359104506059127 · Cited by 13
Stress responses in children after maternal glucocorticoids
Challis, J. R. G. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.183 · Cited by 7
Research works printed but not linked: 6
- David, 2009, Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression, Neuron, 62, 479, 10.1016/j.neuron.2009.04.017 · DOI · Paper page
- Denny, 2012, 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning, Hippocampus, 22, 1188, 10.1002/hipo.20964 · DOI
- Ennaceur, 1988, A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data, Behav. Brain Res., 31, 47, 10.1016/0166-4328(88)90157-X · DOI · Paper page
- Goeden, 2013, Ex vivo perfusion of mid-to-late-gestation mouse placenta for maternal-fetal interaction studies during pregnancy, Nat. Protoc., 8, 66, 10.1038/nprot.2012.144 · DOI
- Tanaka, 2006, Multidirectional and multizonal tangential migration of GABAergic interneurons in the developing cerebral cortex, Development, 133, 2167, 10.1242/dev.02382 · DOI
- Yadav, 2009, A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure, Cell, 138, 976, 10.1016/j.cell.2009.06.051 · DOI · Paper page
Cited by
Sorted by citations
Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., Zeng, L., Chen, J., Fan, S., Du, X., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.44 · Cited by 2,023
Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044
New insights into the biology of osteocalcin
Zoch, M. L., Clemens, T. L., & Riddle, R. C. (2015) · Bone · doi:10.1016/j.bone.2015.05.046 · Cited by 612
Han, Y., You, X., Xing, W., Zhang, Z., & Zou, W. (2018) · Bone Research · doi:10.1038/s41413-018-0019-6 · Cited by 598
Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise
Mera, P., Laue, K., Ferron, M., Confavreux, C. B., Wei, J., Galán-Díez, M., Lacampagne, A., Mitchell, S. J., Mattison, J. A., Chen, Y., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.004 · Cited by 438
Self-citation
Metadata
- 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
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 155
- Issue
- 1
- Pages
- 228-241
- ISSN
- 0092-8674 (ISSN-L)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
