The DOI matches its Crossref record; 51 of the 54 references it cites were found in a registry or an index.
Leptin Regulates Bone Formation via the Sympathetic Nervous System
Open accessAbstract
We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“leptin deficiency lowers sympathetic tone, leading to higher bone mass, while β-adrenergic blockade or leptin replacement during disuse mitigates bone loss by boosting osteoblast activity, curbing osteoclast function, and maintaining leptin levels to preserve bone density and formation rates [80,81]”
From Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies (2026) · cites this paper as [80]
Citations
Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,344
Williams Textbook of Endocrinology
Melmed, S., & Polonsky, K. S. (2016) · Elsevier eBooks · doi:10.1016/c2013-0-15980-6 · Cited by 3,715
Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496
mouse brain in stereotaxic coordinates
Franklin, K. B. J., & Paxinos, G. (1997) · Cited by 3,258
Bone Histomorphometry : Standardization of Nomenclature, Symbols, and Units
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · Cited by 3,258
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356
Leptin 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-citationRole of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,924
Brain Lesions, Obesity, and Other Disturbances in Mice Treated with Monosodium Glutamate
Olney, J. (1969) · Science · doi:10.1126/science.164.3880.719 · Cited by 1,885
Ahima, R. S., & Flier, J. S. (2000) · Annual Review of Physiology · doi:10.1146/annurev.physiol.62.1.413 · Cited by 1,428
Current Protocols in Molecular Biology
(2018) · Current Protocols in Molecular Biology · doi:10.1002/(issn)1934-3647 · Cited by 1,395
Hypothalamic CART is a new anorectic peptide regulated by leptin
Kristensen, P. L., Judge, M. E., Thim, L., Ribel, U., Christjansen, K. N., Wulff, B. S., Clausen, J. T., Jensen, P. B., Madsen, O. D., Vrang, N., et al. (1998) · Nature · doi:10.1038/29993 · Cited by 1,282
Williams Textbook of Endocrinology
Stoffer, S. S. (1999) · JAMA · doi:10.1001/jama.281.9.851 · Cited by 1,245
Riggs, B. L., Khosla, S., & Melton, L. J. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.5.763 · Cited by 1,161
A frameshift mutation in MC4R associated with dominantly inherited human obesity
Yeo, G. S. H., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., & O'Rahilly, S. (1998) · Nature Genetics · doi:10.1038/2404 · Cited by 1,159
A frameshift mutation in human MC4R is associated with a dominant form of obesity
Vaisse, C., Clément, K., Guy-grand, B., & Froguel, P. (1998) · Nature Genetics · doi:10.1038/2407 · Cited by 1,091
Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor
Lu, D., Willard, D. H., Patel, I. R., Kadwell, S. H., Overton, L. K., Kost, T., Luther, M., Chen, W., Woychik, R. P., Wilkison, W. O., et al. (1994) · Nature · doi:10.1038/371799a0 · Cited by 1,075
DNA binding of the glucocorticoid receptor is not essential for survival
Reichardt, H. M., Kaestner, K. H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81183-6 · Cited by 1,068
Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.
Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8878 · Cited by 1,033
Effects of weight and body mass index on bone mineral density in men and women: The framingham study
Felson, D. T., Zhang, Y., Hannan, M. T., & Anderson, J. J. (1993) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650080507 · Cited by 987
Leptin Differentially Regulates NPY and POMC Neurons Projecting to the Lateral Hypothalamic Area
Elias, C. F., Aschkenasi, C., Lee, C., Kelly, J., Ahima, R. S., Bjorbæk, C., Flier, J. S., Saper, C. B., & Elmquist, J. K. (1999) · Neuron · doi:10.1016/s0896-6273(01)80035-0 · Cited by 924
A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic developmentPreprint
Ducy, P. F., Starbuck, M., Priemel, M., Shen, J., Pinero, G. J., Geoffroy, V., Amling, M., & Karsenty, G. (1999) · Genes & Development · doi:10.1101/gad.13.8.1025 · Cited by 772
Self-citationFei, H., Okano, H. J., Li, C., Lee, G.-H., Zhao, C., Darnell, R., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.7001 · Cited by 766
Miller, M. W., Duhl, D. M. J., Vrieling, H., Cordes, S. P., Ollmann, M. M., Winkes, B. M., & Barsh, G. S. (1993) · Genes & Development · doi:10.1101/gad.7.3.454 · Cited by 430
Ikeda, Y., Luo, X., Abbud-Antaki, R., Nilson, J. H., & Parker, K. L. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.4.7659091 · Cited by 429
Self-citationVirus-Assisted Mapping of Neural Inputs to a Feeding Center in the Hypothalamus
DeFalco, J., Tomishima, M. J., Liu, H., Zhao, C., Cai, X., Marth, J. D., Enquist, L. W., & Friedman, J. M. (2001) · Science · doi:10.1126/science.1056602 · Cited by 423
Regulation of Adenylyl Cyclase-Coupled beta-Adrenergic Receptors
Benovic, J., Bouvier, M., Caron, M. G., & Lefkowitz, R. J. (1988) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.04.110188.002201 · Cited by 395
Kaufman, J., Taelman, P., Vermeulen, A., & Vandeweghe, M. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.74.1.1727808 · Cited by 314
Saldanha, C. J., Tuerk, M. J., Kim, Y., Fernandes, A. O., Arnold, A. P., & Schlinger, B. A. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000807)423:4 · Cited by 245
Self-citationRossert, J., Eberspaecher, H., & Crombrugghe, B. D. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.129.5.1421 · Cited by 235
Dissociation between bone resorption and bone formation in osteopenic transgenic mice
Corral, D. A., Amling, M., Priemel, M., Loyer, E. M., Fuchs, S., Ducy, P. F., Baron, R., & Karsenty, G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13835 · Cited by 231
Self-citationSatoh, N., Ogawa, Y., Katsuura, G., Numata, Y., Tsuji, T., Hayase, M., Ebihara, K., Masuzaki, H., Hosoda, K., Yoshimasa, Y., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1787 · Cited by 223
Trémollières, F., Pouillès, J. M., & Ribot, C. A. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.3.8370689 · Cited by 213
Leptin induction of UCP1 gene expression is dependent on sympathetic innervation
Scarpace, P. J., & Matheny, M. E. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.2.e259 · Cited by 203
Localization of gold in mouse brain in relation to gold thioglucose obesity
Debons, A. F., Silver, L., Cronkite, E. P., Johnson, H. A., Brecher, G., Tenzer, D., & Schwartz, I. L. (1962) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1962.202.4.743 · Cited by 197
Restoration of Norepinephrine and Reversal of Phenotypes in Mice Lacking Dopamine β‐Hydroxylase
THOMAS, S. A., Marck, B. T., Palmiter, R. D., & Matsumoto, A. M. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70062468.x · Cited by 188
Asnicar, M., Smith, D. P., Yang, D. D., Heiman, M. L., Fox, N. W., Chen, Y.-F., Hsiung, H. M., & Koster, A. M. (2001) · Endocrinology · doi:10.1210/endo.142.10.8416 · Cited by 177
Corticosteroid actions in hippocampus require DNA binding of glucocorticoid receptor homodimers
Karst, H., Karten, Y. J. G., Reichardt, H. M., de Kloet, E. R., Schütz, G., & Joëls, M. (2000) · Nature Neuroscience · doi:10.1038/79910 · Cited by 171
Magnitude and Impact of Osteoporosis and Fractures
Melton, L. J., & Cooper, C. C. (2001) · Elsevier eBooks · doi:10.1016/b978-012470862-4/50022-2 · Cited by 171
The MONA LISA hypothesis in the time of leptin.
Bray, G. A., & York, D. A. (1998) · PubMed · Cited by 166
Molecular properties of the PTH/PTHrP receptor
Gardella, T. J., & Jüppner, H. (2001) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00409-x · Cited by 163
Dopamine β-hydroxylase deficiency impairs cellular immunity
Alaniz, R. C., THOMAS, S. A., Pérez‐Melgosa, M., Mueller, K., Farr, A. G., Palmiter, R. D., & Wilson, C. B. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2274 · Cited by 155
Corticosteroid-induced osteoporosis
Adachi, J. D., Bensen, W., & Hodsman, A. B. (1993) · Seminars in Arthritis and Rheumatism · doi:10.1016/s0049-0172(05)80029-0 · Cited by 152
Effects of propranolol on bone metabolism in the rat
Minkowitz, B., Boskey, A. L., Lane, J. M., Pearlman, H. S., & Vigorita, V. J. (1991) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100090613 · Cited by 107
Ruffin, M.-P., & Nicolaidis, S. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01922-8 · Cited by 101
New Treatments for Reflex Sympathetic Dystrophy
Schwartzman, R. J. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008313430911 · Cited by 96
Bliziotes, M. M., McLoughlin, S. W., Gunness, M. E., Fumagalli, F., Jones, S. R., & Caron, M. G. (2000) · Bone · doi:10.1016/s8756-3282(99)00232-x · Cited by 81
Specific depletion of body fat in parabiotic partners of tube-fed obese rats
Harris, R. B., & Martin, R. J. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.247.2.r380 · Cited by 60
Magnitude and Impact of Osteoporosis and Fractures
Marcocci, C., Cetani, F., Vignali, E., & Pinchera, A. (2006) · CRC Press eBooks · doi:10.1201/b14631-2 · Cited by 43
Research works printed but not linked: 1
- Tremollieres, 1993, Vertebral postmenopausal bone loss is reduced in overweight women, J. Clin. Endocrinol. Metab., 77, 683
Cited by
Sorted by citations
Physiology and Pathophysiology of Purinergic Neurotransmission
Burnstock, G. (2007) · Physiological Reviews · doi:10.1152/physrev.00043.2006 · Cited by 1,609
The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review
Klok, M. D., Jakobsdottir, S., & Drent, M. L. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2006.00270.x · Cited by 1,442
Control of osteoblast function and regulation of bone mass
Harada, S.-I., & Rodan, G. A. (2003) · Nature · doi:10.1038/nature01660 · Cited by 1,478
Chronic Kidney Disease: Effects on the Cardiovascular System
Schiffrin, E. L., Lipman, M. L., & Mann, J. F. E. (2007) · Circulation · doi:10.1161/circulationaha.106.678342 · Cited by 1,448
Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone Marrow
Katayama, Y., Battista, M., Kao, W.-M., Hidalgo, A., Peired, A. J., Thomas, S. A., & Frenette, P. S. (2006) · Cell · doi:10.1016/j.cell.2005.10.041 · Cited by 1,412
Metadata
- Authors
- Takeda, S., Elefteriou, F., Levasseur, R., Liu, X., Zhao, L., Parker, K. L., Armstrong, D., Ducy, P., & Karsenty, G.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Baylor College of Medicine (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 111
- Issue
- 3
- Pages
- 305-317
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2147510409
- Cited by
- 1,735
- References
- 54
- Citations by year
- 2026: 50 · 2025: 58 · 2024: 61 · 2023: 49 · 2022: 55 · 2021: 57 · 2020: 69 · 2019: 70 · 2018: 66 · 2017: 68 · 2016: 66 · 2015: 81 · 2014: 86 · 2013: 71 · 2012: 105
- FWCI
- 23.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-54480, R01DK058883, R01DK054480, DK58883)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD24054)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- leptin, bone formation, sympathetic nervous system, beta-adrenergic receptors, osteoblast proliferation, leptin resistance, leptin deficiency, hypothalamic neurons, osteoporosis, bone mass, ovariectomy
- MeSH terms
- Adrenergic beta-Antagonists, Animals, Cells, Cultured, Hypothalamus, Mice, Inbred C57BL, Neuropeptides, Obesity, Oligopeptides, Osteoblasts, Osteogenesis, Pyrrolidonecarboxylic Acid, Receptors, Adrenergic, beta, Sympathetic Nervous System, Receptors, Corticotropin, Leptin, Receptor, Melanocortin, Type 4, Mice, Receptors, Leptin
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
