Cited by 1,311Bone Metabolism and DiseasesBone health and osteoporosis researchRegulation of Appetite and Obesity

The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.

Leptin regulation of bone resorption by the sympathetic nervous system and CART

Elefteriou, Florent, Ahn, Jong Deok, Takeda, Shu, Starbuck, Michael, Yang, Xiangli, Liu, Xiuyun, Kondo, Hisataka, Richards, William G., Bannon, Tony W., Noda, Masaki, Clement, Karine, Vaisse, Christian, Karsenty, Gerard·2005·Nature

DOI 10.1038/nature03398

Open this paper in CoChat — free account

Abstract

Bone remodelling, the mechanism by which vertebrates regulate bone mass, comprises two phases, namely resorption by osteoclasts and formation by osteoblasts; osteoblasts are multifunctional cells also controlling osteoclast differentiation. Sympathetic signalling via beta2-adrenergic receptors (Adrb2) present on osteoblasts controls bone formation downstream of leptin. Here we show, by analysing Adrb2-deficient mice, that the sympathetic nervous system favours bone resorption by increasing expression in osteoblast progenitor cells of the osteoclast differentiation factor Rankl. This sympathetic function requires phosphorylation (by protein kinase A) of ATF4, a cell-specific CREB-related transcription factor essential for osteoblast differentiation and function. That bone resorption cannot increase in gonadectomized Adrb2-deficient mice highlights the biological importance of this regulation, but also contrasts sharply with the increase in bone resorption characterizing another hypogonadic mouse with low sympathetic tone, the ob/ob mouse. This discrepancy is explained, in part, by the fact that CART ('cocaine amphetamine regulated transcript'), a neuropeptide whose expression is controlled by leptin and nearly abolished in ob/ob mice, inhibits bone resorption by modulating Rankl expression. Our study establishes that leptin-regulated neural pathways control both aspects of bone remodelling, and demonstrates that integrity of sympathetic signalling is necessary for the increase…

Integrity signals

Registry

Crossref · 10.1038/nature03398

Cites

17 of 17 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
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 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-citation
Leptin 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-citation
Genetic regulation of osteoclast development and function
Teitelbaum, S. L., & Ross, F. P. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1122 · Cited by 1,720
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
OSTEOBLASTIC CELLS ARE INVOLVED IN OSTEOCLAST FORMATION
Takahashi, N., Akatsu, T., Udagawa, N., Sasaki, T., Yamaguchi, A., Moseley, J. M., Martin, T. J., & Suda, T. (1988) · Endocrinology · doi:10.1210/endo-123-5-2600 · Cited by 934
ATF4 Is a Substrate of RSK2 and an Essential Regulator of Osteoblast Biology
Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H. C., Schinke, T., Li, L., Brancorsini, S., Sassone‐Corsi, P., Townes, T. M., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00344-7 · Cited by 822
Self-citation
Two Distinct Osteoblast-Specific cis-Acting Elements Control Expression of a Mouse Osteocalcin Gene
Ducy, P. F., & Karsenty, G. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.4.1858 · Cited by 570
Self-citation

Flagged first, then by citations

Show all 17 references

Sorted by citations

Items 901–999 of 999

Both NPY-Expressing and CART-Expressing Neurons Increase Energy Expenditure and Trabecular Bone Mass in Response to AP1 Antagonism, But Have Opposite Effects on Bone Resorption
Idelevich, A., Sato, K., Avihai, B., Nagano, K., Galien, A., Rowe, G. C., Gori, F., & Baron, R. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3967 · Cited by 7
“On the other hand, mice devoid of CART have a normal appetite, but display bone loss, due to increased resorption.((18)) MC4R−/− mice display increased bodyweight and high bonemass, whereas mutation of this receptor in humans also contributes to the development of obesity.”
BackgroundInfluential
The effect of bariatric surgery on bone Health: From mechanism to management
Ye, Y., Yang, D., & Han, J. (2020) · Obesity Medicine · doi:10.1016/j.obmed.2020.100199 · Cited by 7
Bacterial stress response: understanding the molecular mechanics to identify possible therapeutic targets
Kumar, A., Rahal, A., Sohal, J. S., & Gupta, V. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2020.1813021 · Cited by 7
Exercise-induced hypercalcemia and vasopressin-mediated bone resorption
Senda, M., Hamano, T., Fujii, N., Ito, T., Sakaguchi, Y., Matsui, I., Isaka, Y., & Moriyama, T. (2021) · Osteoporosis International · doi:10.1007/s00198-021-06030-1 · Cited by 8
eIF2α–ATF4 Pathway Activated by a Change in the Calcium Environment Participates in BCP-Mediated Bone Regeneration
Xiang, Z., Wu, Q., Wang, Y., Wang, P., He, Y., & Li, J. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.0c01802 · Cited by 7
The impact and mechanism of nerve injury on bone metabolism
Zhang, Y., Zhao, X. X., Ge, D., Huang, Y., & Yao, Q. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149699 · Cited by 8
Participación del sistema nervioso y del tracto gastrointestinal en la homeostasis energética
Solomon, A., & Martínez, J. A. (2016) · Revista de medicina de la Universidad de Navarra · doi:10.15581/021.50.7598 · Cited by 7
Store-operated calcium entry induced by activation of Gq-coupled alpha1B adrenergic receptor in human osteoblast
Kodama, D., & Togari, A. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.06.047 · Cited by 7
Regulation of Calcium and Phosphate Metabolism
Conigrave, A. D. (2012) · Springer eBooks · doi:10.1007/978-1-4419-5550-0_2 · Cited by 9
“In the periphery, b 2 -adrenergic receptors on osteoblasts suppress proliferation and promote the expression of RANK-L and, thus, induce osteoclastogenesis and bone resorption ( [ 235 ] ; review: [ 201 ] ).”
Background
Voluntary wheel running mitigates the stress-induced bone loss in ovariectomized rats
Lertsinthai, P., Charoenphandhu, J., Suntornsaratoon, P., Krishnamra, N., & Charoenphandhu, N. (2014) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-014-0597-3 · Cited by 7
“Specifically, the hypothalamus regulates bone remodeling and reduces bone mass through leptin which modulates the sympathetic b2-adrenergic receptor signaling pathway [33].”
Background
The hunger games of skeletal metabolism
Wee, N. K. Y., & Baldock, P. A. J. (2014) · BoneKEy Reports · doi:10.1038/bonekey.2014.83 · Cited by 7
“Functional b2-adrenergic receptors were identified on murine and human osteoblasts(3) and the administration of a b2-blocker to WT mice resulted in increased cancellous bone mass.(27,47) No change in cancellous bone mass was found when b2-adrenergic receptor-deficient mice were given an intracerebroventricular (i.”
Background
Adrenergic stimulation decreases osteoblast oxytocin synthesis
Cuscito, C., Colaianni, G., Tamma, R., Greco, G., Dell'Endice, S., Yuen, T., Sun, L., Zaidi, M., Benedetto, A. D., & Zallone, A. Z. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06235.x · Cited by 7
The Time Point-Specific Effect of Beta-Adrenergic Blockade in Attenuating High Fat Diet-Induced Obesity and Bone Loss
Baek, K., Kang, J., Lee, J., Kim, M., & Baek, J. (2018) · Calcified Tissue International · doi:10.1007/s00223-018-0407-3 · Cited by 7
“Multiple in vitro and in vivo studies have shown that SNS activation drives bone loss mainly by reducing osteoblastogenesis and bone formation [2], and by stimulating osteoclastogenesis and bone resorption [3].”
Background
Thyrotoxicosis Involves β2-Adrenoceptor Signaling to Negatively Affect Microarchitecture and Biomechanical Properties of the Femur
Neofiti-Papi, B., Albuquerque, R. P. E., Miranda-Rodrigues, M., Gonçalves, N. J. N., Jorgetti, V., Brum, P. C., Ferreira, J. C. B., & Gouveia, C. H. D. A. (2019) · Thyroid · doi:10.1089/thy.2018.0259 · Cited by 7
“…mass (HBM) phenotype in mice deﬁcient in dopamine b -hydroxylase (DbH - / - ), the limiting enzyme responsible for the synthesis of catecholamines (10), and in mice with global (11) and osteoblast-speciﬁc (12) gene inactivation of b 2-AR ( b 2-AR - / - and b 2 osb -AR - / - mice, respectively).”
Influential
Systemic bone loss following myocardial infarction in mice
Tjandra, P. M., Paralkar, M. P., Osipov, B., Chen, Y., Zhao, F., Ripplinger, C. M., & Christiansen, B. (2020) · Journal of Orthopaedic Research® · doi:10.1002/jor.24867 · Cited by 7
“While all three β-adrenergic receptors are present in the skeletal system, β2 is prevalently expressed in both osteoblasts and osteoclasts [18, 21-28].”
Background
Intricate coupling between the transactivation and basic-leucine zipper domains governs phosphorylation of transcription factor ATF4 by casein kinase 2
Siang, S., Underbakke, E. S., & Roche, J. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101633 · Cited by 8
“The primary phosphorylation sites of protein kinase A (PKA) (17), ribosomal S6 kinase 2 (RSK2) (18), casein kinase 2 (CK2) (19), and RET tyrosine kinase (20), among others, are all known to be localized within the TAD of ATF4.”
Background
Osteoporosis in Spaceflight
Iwase, S., Nishimura, N., & Mano, T. (2013) · InTech eBooks · doi:10.5772/54708 · Cited by 9
Semaphorinï¿½3A enhances osteogenesis of MG63 cells through interaction with Schwann cells inï¿½vitro
Yu, H., Pei, T., Ren, J., Ding, Y., Wu, A., & Zhou, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8628 · Cited by 7
“Sema3A completes its biological function via binding to a receptor complex encompassing ligand-binding component Neuropilin (Nrp) 1 and class A Plexins (Plx) a 1, 2, 3 and 4, the latter of which is necessary for proper signal transduction (16).”
Pathophysiologie und Pathomorphologie der Osteoporose
Priemel, M., Münch, C., Beil, F. T., Ritzel, H., & Amling, M. (2006) · Der Radiologe · doi:10.1007/s00117-006-1413-4 · Cited by 8
Childhood fractures: Time to implement strategies to reduce these events
Goulding, A. (2007) · International Congress Series · doi:10.1016/j.ics.2006.08.022 · Cited by 7
Update on the transcriptional control of osteoblast differentiation
Karsenty, G. (2007) · BoneKEy-Osteovision · doi:10.1138/20070262 · Cited by 7
“ATF4 does not only regulate bone formation but also expression in osteoblasts of TNF11, a gene encoding the key osteoclast differentiation factor, RANK ligand (29).”
BackgroundSelf-citation
Skeletal morphofunctional considerations and the pituitary-thyroid axis
considerations, S. M. (2009) · Frontiers in Bioscience-Scholar · doi:10.2741/s9 · Cited by 6
Commentary: Parallel Evolution ofMolecular Endocrinologyas a Journal and a Discipline: Convergence of Interests with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH)
Margolis, R., & Smith, P. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0168 · Cited by 7
“At first only studied in the context of obesity, the identification of receptors for leptin and their localization in areas of the brain, further linked leptin to food intake, body composition, and reproduction (4, 8).”
Background
Deciphering the skeletal interoceptive circuitry to control bone homeostasis
Wu, Y., Guo, J., Chen, Z., Zhang, F., Chow, B., Chen, Z., Yeung, K., & Qiao, W. (2025) · BMEMat · doi:10.1002/bmm2.12138 · Cited by 6
β2-Adrenergic receptor regulates osteoblast differentiation and migration and C-terminal β-catenin phosphorylation
Worton, L. E., Curtin, A. C., & Gardiner, E. M. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152490 · Cited by 6
Brown fat-specific mitoribosomal function is crucial for preventing cold exposure-induced bone loss
Tian, J., Moon, J. S., Nga, H. T., Lee, H. Y., Nguyen, T. L., Jang, H. J., Setoyama, D., Shong, M., Lee, J. H., & Yi, H. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05347-4 · Cited by 6
Unraveling the Mechanism of Impaired Osteogenic Differentiation in Osteoporosis: Insights from ADRB2 Gene Polymorphism
Krasnova, O. A., Sopova, J. V., Kovaleva, A., Semenova, P. I., Zhuk, A. S., Smirnova, D., Perepletchikova, D. A., Bystrova, O. A., Martynova, M. G., Karelkin, V. V., et al. (2024) · Cells · doi:10.3390/cells13242110 · Cited by 6
Association of body composition with predicted hip bone strength among Chinese postmenopausal women: a longitudinal study
Shi, X., Deng, Y., Kang, H., Liu, M., Chen, Y., & Xiao, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-42031-1 · Cited by 6
Bone regeneration in rat using polycaprolactone/gelatin/epinephrine scaffold
Ehterami, A., Khastar, H., Soleimannejad, M., Salehi, M., Nazarnezhad, S., Ghatar, J. M., Bit, A., Jafarisani, M., Abbaszadeh‐Goudarzi, G., & Shariatifar, N. (2021) · Drug Development and Industrial Pharmacy · doi:10.1080/03639045.2022.2070640 · Cited by 6
Type 2 Diabetes and Bone Disease
López, N., Cohen, S. M., & Emanuele, M. (2023) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-023-09288-7 · Cited by 6
“Leptin also has an impact on bone mass—it controls the proliferation and function of osteoblasts through a hypothalamic neuron loop and two neural outputs [78, 79].”
Background
A systems approach to bone pathophysiology
Weiss, A., Lipshtat, A., & Mechanick, J. I. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05816.x · Cited by 6
Sympathetic Skin Response and Vasomotor Symptoms in Postmenopausal Osteoporotic Women.
Ashraf, A., Roshanzamir, S., Bemana, G., Mohammadi, A., Jahani, N., & Naseri, M. (2015) · PubMed Central · Cited by 6
Obesity and osteoporosis
Shishkova, V. N., & Shishkova, V. N. (2011) · Osteoporosis and Bone Diseases · doi:10.14341/osteo2011121-26 · Cited by 6
The Sensory and Sympathetic Nervous System in Cartilage Physiology and Pathophysiology
Grässel, S., Straub, R. H., & Jenei‐Lanzl, Z. (2017) · Springer eBooks · doi:10.1007/978-3-319-45803-8_9 · Cited by 6
Energy Homeostasis and Obesity: The Therapeutic Role of Anorexigenic and Orexigenic Peptide
Patel, C. A., & Acharya, S. R. (2018) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-018-9740-7 · Cited by 6
Sympathetic nervous system contributes to orthodontic tooth movement by central neural regulation from hypothalamus.
Cao, H., Fang, B., Wang, X., & Zhou, Y. (2020) · PubMed · doi:10.14670/hh-18-280 · Cited by 6
“More importantly, along with the first report of regulation of bone formation by SNS upon the interaction of leptin, which provided direct evidence of the participation of SNS in bone metabolism, the regulatory effect of SNS on bone metabolism has become a focus in the research field of bone metabolism (Ducy et al., 2…”
BackgroundInfluential
Selective β2-Adrenoceptor Blockade Rescues Mandibular Growth Retardation in Adolescent Rats Exposed to Chronic Intermittent Hypoxia
Hong, H., Hosomichi, J., Maeda, H., Ishida, Y., Usumi‐Fujita, R., Yoshida, K., & Ono, T. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.676270 · Cited by 6
The effect of chemical sympathectomy and stress on bone remodeling in adult rats.
Hu, K., Zhou, H., Zhang, G., Qin, R., Hou, R., Kong, L., & Ding, Y. (2010) · PubMed · Cited by 6
Links Between Hypertension and Osteoporosis: Benidipine Ameliorates Osteoporosis in Ovariectomized Hypertensive Rats Through Promotion of Osteoblast Proliferation and Inhibition of Osteoclast Differentiation
Shimizu, H., Nakagami, H., Yasumasa, N., Osako, M. K., Kyutoku, M., Koriyama, H., Nakagami, F., Shimamura, M., Rakugi, H., & Morishita, R. (2012) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-012-0248-y · Cited by 6
Protein nutrition as therapy for a genetic disorder of bone?
Martin, T. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.11.007 · Cited by 6
Chapter 10. Neuronal Regulation of Bone Remodeling
Karsenty, G., & Elefteriou, F. (2008) · Wiley eBooks · doi:10.1002/9780470623992.ch10 · Cited by 5
Self-citation
Allometric description of ostrich (Struthio camelus var. domesticus) growth and development
Kritzinger, W. J. (2011) · SUNScholar (Stellenbosch University) · Cited by 6
The Central Network Involved in the Processing of Vestibular Inputs and the Generation of Vestibulosympathetic Reflexes Controlling Blood Pressure in Humans
McCarthy, B., Henderson, L. A., & Macefield, V. G. (2023) · Comprehensive physiology · doi:10.1002/j.2040-4603.2023.tb00270.x · Cited by 5
“The bone-forming cells (osteoblasts) express beta 2-adrenergic receptors, the stimulation of which leads to bone loss (57).”
Investigating the effect of neuro-immune communication on immune responses in health and disease: Exploring immunological disorders
Hesampour, F., Bernstein, C. N., & Ghia, J. (2025) · Cellular Immunology · doi:10.1016/j.cellimm.2025.104963 · Cited by 5
Study of the biological relevance of Wnt/β-catenin signaling pathway and β-adrenergic regulation in osteoblastic differentiation of mesenchymal stem cells
Yarahmadi, H. B., Khani, A., Baghdadchi, Y., Javadi, M., Sharafi, A., Sohi, A. N., & Kheiri, H. R. (2022) · Gene Reports · doi:10.1016/j.genrep.2022.101662 · Cited by 5
Heart Failure and Osteoporosis: Shared Challenges in the Aging Population
Spoladore, R., Ciampi, C. M., Ossola, P., Sultana, A., Spreafico, L. P., Farina, A., & Fragasso, G. (2025) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd12020069 · Cited by 5
“Adrenergic signaling, especially through β 2-adrenergic receptors ( β 2-AR), has been shown to influence bone remodeling by modulating RANKL expression [48–50].”
A transcriptome-wide association study to detect novel genes for volumetric bone mineral density
Liu, A., Liu, Y., Su, K., Greenbaum, J., Bai, Y., Tian, Q., Zhao, L., Deng, H., & Shen, H. (2021) · Bone · doi:10.1016/j.bone.2021.116106 · Cited by 5
β2-adrenoceptors kick osteoarthritis – Time to rethink prevention and therapy
Jenei‐Lanzl, Z., & Straub, R. H. (2024) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2024.06.012 · Cited by 5
Beta Adrenergic Receptor Stimulation Suppresses Cell Migration in Association with Cell Cycle Transition in Osteoblasts—Live Imaging Analyses Based on FUCCI System
Katsumura, S., Ezura, Y., Izu, Y., Shirakawa, J., Miyawaki, A., Harada, K., & Noda, M. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.25096 · Cited by 6
Self-citation
Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells
Ezura, Y., Nagata, J., Nagao, M., Hemmi, H., Hayata, T., Rittling, S. R., Denhardt, D. T., & Noda, M. (2014) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-014-0568-8 · Cited by 5
Self-citation
FIAT control of osteoblast activity
St‐Arnaud, R., & Mandic, V. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22435 · Cited by 5
“Control of Rankl transcription by ATF4 is regulated through phosphorylation of residue serine 254 by protein kinase A (PKA) [Elefteriou et al., 2005].”
Background
The effect of neural cell integrated into 3D co-axial bioprinted BMMSC structures during osteogenesis
Zhang, Y., Chen, H., Long, X., & Xu, T. (2021) · Regenerative Biomaterials · doi:10.1093/rb/rbab041 · Cited by 6
“As sensory and sympathetic neurons are well known to innervate the marrow cavity, trabecular bone and periosteum of long bones [22], it is difficult to observe the neural regulation of bone remodeling and healing.”
Background
Fat Mass as an Independent Variable to Assess the Possibility of Predicting the Stability in Postmenopausal Women with and Without Osteoporosis
Mofid, M., Mohebi, S., Darbani, M., Basiri, Z., Naderifar, H., & Torkaman, G. (2022) · Muscles Ligaments and Tendons Journal · doi:10.32098/mltj.03.2022.10 · Cited by 5
“This signaling pathway activates osteoclast differentiation, which leads to increased bone resorption (30).”
Background
Foot bone density in diabetes may be unaffected by the presence of neuropathy
Barwick, A., Tessier, J., de Jonge, X. J., & Chuter, V. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.04.013 · Cited by 5
Sex- and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus
Blasio, M. J. D., Lanham, S., Blache, D., Oreffo, R. O. C., Fowden, A. L., & Forhead, A. J. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00351.2017 · Cited by 4
“In contrast, it has also been reported in rodents and sheep that leptin 80 can suppress bone formation indirectly by hypothalamic control of sympathetic and cocaine 81 amphetamine regulated transcript (CART) pathways (12, 13, 40, 49).”
Background
Gestational Diabetes Mellitus Prediction Based on Two Classification Algorithms
Zhong, W., Jiang, S., Wu, W., Peng, D., Xu, T., Wang, J., & Wang, G. (2019) · International Congress on Image and Signal Processing (CISP) · doi:10.1109/cisp-bmei48845.2019.8965819 · Cited by 5
“Choose CART algorithm [10] as decision tree algorithm.”
Method
Use of beta-blockers and risk of aseptic loosening in total hip and knee arthroplasty: a nested case - control study.
de Soto, P. C. M., Tamimi, I., Bautista-Enrique, D., Bravo-Zurita, M. J., Cáceres, A. G., Tamimi, F., & Dawid-Milner, M. S. (2019) · Europe PMC (PubMed Central) · Cited by 5
Adipokines and Metabolism
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_24 · Cited by 5
Regeneration of Musculoskeletal Tissues
Stocum, D. L. (2006) · Elsevier eBooks · doi:10.1016/b978-012369371-6/50026-5 · Cited by 5
Bivariate whole-genome linkage scan for bone geometry and total body fat mass
Lei, S., Deng, F., Xiao, P., Zhong, K., Deng, H., Recker, R. R., & Deng, H. (2009) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/s1673-8527(08)60095-8 · Cited by 5
Leptin's RIGHT Turn to the Brain Stem
Rosen, C. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.001 · Cited by 5
“Work by the Karsenty group and others detailed the cellular and molecular targets of b2 adrenergic activation and the role leptin played in mediating these downstream events (Elefteriou et al., 2005; Fu et al., 2005).”
Background
Progress in Lipid Research
Hodson, L., & Fielding, B. A. (2013) · Cited by 5
Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss
Richard, S., Torabi, N., Valverde-Franco, G., Tremblay, G. A., Chen, T., Vogel, G., Morel, M., Cléroux, P., Komarova, S. V., Tremblay, M. L., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010074.eor · Cited by 6
Regulation of Male Fertility by BonePreprint
Karsenty, G. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010934 · Cited by 5
“2006), two pituitary hormones, as regulators of bone mass; and the realization that bone formation and bone resorption are regulated by the sympathetic nervous system (Takeda et al. 2002; Elefteriou et al. 2005).”
BackgroundInfluentialSelf-citation
Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations
Zhang, X., Tian, L., Majumdar, A., & Scheller, E. L. (2024) · Comprehensive physiology · doi:10.1002/cphy.c230016 · Cited by 23
β2-adrenoceptor signaling in chondrocytes regulates long bone growth, bone homeostasis, and fracture healing in mice
Kuhn, M. R., Haffner‐Luntzer, M., Dieterich, S., Sachs, M., Rösch, G., Jenei‐Lanzl, Z., Reber, S. O., Ignatius, A. A., & Tschaffon, M. E. A. (2026) · JBMR Plus · doi:10.1093/jbmrpl/ziag021 · Cited by 4
“…evidence for this is given by the fact that mice with a systemic or an osteoblast-specific lack of this receptor have an increased bone mass. 16,18 In this study, the aim was to analyze the influence of a chondrocyte-specific knockout of the β 2 -AR on long bone growth , bone homeostasis ,…”
Deciphering inter-organ communication: The multi-organ-bone axis in osteoporosis and emerging therapeutic strategies
Wen, R., Wang, H., & Wang, S. (2026) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2026.101119 · Cited by 4
“Elefteriou et al. confirmed that leptin exerts an inhibitory effect on OB via the hypothalamic-sympathetic nervous pathway, a process strictly dependent on the structural integrity of the sympathetic nervous system (SNS) [33].”
Impact of Pheochromocytoma or Paraganglioma on Bone Metabolism: A Systemic Review and Meta-analysis
Dutta, D., Nagendra, L., Chandran, M., Sharma, M., Bhattacharya, S., & Mukhopadhyay, S. (2024) · Journal of Clinical Densitometry · doi:10.1016/j.jocd.2024.101501 · Cited by 4
The autonomic nervous system and bone health in chronic kidney disease
Zoccali, C., Vervloet, M. G., Evenepoel, P., Massy, Z. A., Cozzolino, M. G., Mallamaci, F., Lederer, E. D., Cannata-Andía, J. B., & Drüeke, T. B. (2025) · European Journal of Clinical Investigation · doi:10.1111/eci.70007 · Cited by 4
“…osteoclastogenesis via the release of Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) from osteoblasts (Figure 1), which involves activating transcription factor 4 and protein kinase A. 33 On the other hand, this neurotransmitter is also an established agonist for β 1 receptors.”
Impact of the endocannabinoid system on murine cranial and alveolar bone phenotype
Setiawan, M. F., Jäger, A., Daratsianos, N., Reimann, S., Chen, J., Schmöle, A., Derichs-Schönthal, D., & Konermann, A. (2020) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2020.151516 · Cited by 4
Heart failure and osteoporosis: common pathogenetic components
Skripnikova, I. A., Куруглиевна, Я. Э., & Drapkina, O. M. (2022) · CARDIOVASCULAR THERAPY AND PREVENTION · doi:10.15829/1728-8800-2022-3233 · Cited by 4
Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma
Qi, W., Cui, L., Jiajue, R., Pang, Q., Chi, Y., Liu, W., Jiang, Y., Wang, O., Li, K., Xing, X., et al. (2023) · Journal of Endocrinological Investigation · doi:10.1007/s40618-023-02198-x · Cited by 6
“Disruption of sympathetic signaling leads to a high bone mass phenotype in mice [12].”
The specificities, influencing factors, and medical implications of bone circadian rhythms
Mei, G., Wang, J., Wang, J., Ye, L., Yi, M., Chen, G., Zhang, Y., Tang, Q., & Chen, L. (2024) · The FASEB Journal · doi:10.1096/fj.202302582rr · Cited by 7
“74,191 Du et al. found that bone mass decreased after 2 weeks of cold stimulation, but during this time, increased brown adipose tissue (BAT) promoted osteogenic differentiation and mineralization of BMSCs and inhibited bone resorption, ultimately resulting in bone mass recovery after a month.”
Influential
Pharmacogenetic and microRNA mechanisms of beta blocker use on bone
Lary, C. W., Atkinson, E. J., Spillane, J., Nayema, Z., Roy, T., Peters, R., Scott, G. T., Chen, H., Nagarajan, A., Brown, A., et al. (2024) · Journal of Bone and Mineral Research · doi:10.1093/jbmr/zjae200 · Cited by 4
ATRX silences Cartpt expression in osteoblastic cells during skeletal development
Chen, Y., Jiang, M., Leynes, C., Adeyeye, M., Majano, C. F., Ibrahim, B., Polak, U., Hung, G., Jin, Z., Lanza, D. G., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci163587 · Cited by 4
“Finally, we generated founder mice of Cartpt knockout in the background of Atrx-cKO by CRISPR/Cas9 to further study the epistatic interaction of ATRX and CARTPT on bone mass. Based on micro-CT analysis on these founder mice, Cartpt deletion showed a trend toward to decreased trabecular bone volume in femurs in a dosag…”
Influential
The effect of interval versus continuous exercise on plasma leptin and ghrelin concentration in young trotters
Kowalik, S., & Kędzierski, W. (2011) · Polish Journal of Veterinary Sciences · doi:10.2478/v10181-011-0056-1 · Cited by 4
“Recent studies in humans and horses have suggested that hypoleptinemia could interfere with proper immunity, bone metabolism, and reproductive function (Elefteriou et al. 2005, Montez et. al.”
Background
Effect of rat brain tissue extracts on osteoblast proliferation and differentiation
Huang, G., Ma, X., Xia, X., Jiang, J., Wei-fang, J., Gao, J.-J., & Huang-yuan, H. (2011) · International Orthopaedics · doi:10.1007/s00264-011-1423-3 · Cited by 4
The pathogenesis of Charcot osteoarthropathy: the role of the peripheral nervous system
Radikovich, G. G., & Kaminarskaya, Y. A. (2015) · Endocrine Surgery · doi:10.14341/serg201445-14 · Cited by 4
Endocrinology of bone/brain crosstalk
Metozzi, A., Bonamassa, L., Brandi, G., & Brandi, M. L. (2015) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.2015.979787 · Cited by 4
“In addition to RANKL, other osteoclastogenic factors such as IL-6, IL-11 and PGE2 are stimulated by b-adrenergic agonists in human and mouse osteoblastic cells [121,127], apparently through both PKA and p38 MAPK signaling [121,128].”
Background
FIAT, the factor‐inhibiting ATF4‐mediated transcription, also represses the transcriptional activity of the bZIP factor FRA‐1
St‐Arnaud, R., Mandic, V., & Elchaarani, B. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05211.x · Cited by 4
Sialoglycoprotein isolated from Carassius auratus eggs promotes osteogenesis by stimulating mesenchymal stem cells to commit to osteoblast differentiation
Mao, L., Wang, M., Xi, X., Dai, Y., Wang, N., Wang, J., & Xue, C. (2019) · Cell and Tissue Research · doi:10.1007/s00441-018-2976-x · Cited by 4
Bone Mineral Density in Patients Suffering from Ménière’s Disease
Shupak, A., & Faranesh, N. (2020) · Audiology and Neurotology · doi:10.1159/000506039 · Cited by 4
“These pathways might play a role in both the bone deformity and demineralization demonstrated in adoles cent scoliosis [Elefteriou et al., 2005; Hitier et al., 2015].”
BackgroundInfluential
Sleep disorders and osteoporosis
Swanson, C. M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00060-5 · Cited by 4
Bone metabolism and fracture risk after Biliopancreatic Diversion
Ramos, M. A., Ballesteros-Pomar, M. D., Fondo, A. M. U., González-Herráez, L., de Francisco, T. G., Sierra, M., & Rodríguez, I. M. C. (2021) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2021.06.003 · Cited by 4
The β-Adrenergic System and Bone Mineral Remodeling
González-Rozas, M., Dueñas‐Laita, A., & Pérez‐Castrillón, J. L. (2015) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-015-9183-z · Cited by 4
“are located in the arcuate nucleus, and the deletion of one in animal models results in high bone mass and suppressed resorption [24].”
Influential
Trauma in the Diabetic Limb
Liu, G. T., Sanders, D., Raspovic, K. M., & Wukich, D. K. (2019) · Clinics in Podiatric Medicine and Surgery · doi:10.1016/j.cpm.2019.02.012 · Cited by 5
Neural regulation of the contractility of nutrient artery in the guinea pig tibia
Fukuta, H., Mitsui, R., Takano, H., & Hashitani, H. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02362-9 · Cited by 4
Effects of Systemic Propranolol Application on the New Bone Formation in Periimplant Guided Bone Regeneration
Güneş, N., Gül, M., Dündar, S., Artaş, G., Kobat, M. A., Teki̇n, S., Bozoğlan, A., & Isayev, A. (2021) · Journal of Oral and Maxillofacial Research · doi:10.5037/jomr.2021.12302 · Cited by 4
“Although these receptors are secreted primarily from cardiovascular and respiratory cells, they are also secreted from bone cells such as osteoblasts and osteoclasts [4-6].”
Background
La double vie de la sérotonine ou quand la génétique découvre la physiologie
Oury, F., & Karsenty, G. (2010) · médecine/sciences · doi:10.1051/medsci/2010268-9713 · Cited by 3
“Nous en citerons trois qui n’auraient sans doute pas pu être découvertes autrement : le rôle du tissu adipeux dans le contrôle de l’appétit [1, 2], la régulation de la masse osseuse par le cerveau [3-5] et la régulation du métabolisme énergétique par le squelette [6].”
BackgroundSelf-citation
New Horizons in Skeletal Physiology and Pathophysiology
Zaidi, M., Iqbal, J. Z., & Sun, L. (2010) · Endocrine Practice · doi:10.4158/ep10118.ra · Cited by 4
Clinical Applications of Microneurography
Mano, T. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-386525-0.00081-0 · Cited by 4
18. Diet-induced obesity alters skeletal microarchitecture and the endocrine activity of bone
Wee, N. K. Y., Herzog, H., & Baldock, P. A. J. (2016) · Wageningen Academic Publishers eBooks · doi:10.3920/978-90-8686-823-0_18 · Cited by 4
Bone and the Central Nervous System
Kulkarni, R. N., & Baldock, P. A. J. (2017) · Molecular and integrative toxicology · doi:10.1007/978-3-319-56192-9_13 · Cited by 4
Association between metabolic risks and bone mineral density in postmenopausal women
Seoung, J. Y., Lee, S. W., Kang, Y. M., Kim, M. J., Park, J. M., Moon, H. M., & Rhim, C. C. (2018) · Clinical and Experimental Obstetrics & Gynecology · doi:10.12891/ceog4341.2018 · Cited by 4
The Central Regulation of Bone Mass: Genetic Evidence and Molecular Bases
Karsenty, G. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_378 · Cited by 4
Self-citation
Gene Expression of Adipocytokine Receptors during Osteoblastic Differentiation
Kamada, A., Ikeo, T., Yoshikawa, Y., Domae, E., Goda, S., Tamura, I., Tanabe, K., Tanabe, J., Itsusaki, H., Kinoshita, G., et al. (2009) · Journal of oral tissue engineering · doi:10.11223/jarde.7.53 · Cited by 4
MOLECULAR GENETIC STUDIES OF MELANOCORTIN RECEPTORS IN MORBID OBESITY
Valli‐Jaakola, K. (2007) · Työväentutkimus Vuosikirja · Cited by 4
The Central Network Involved in the Processing of Vestibular Inputs and the Generation of Vestibulosympathetic Reflexes Controlling Blood Pressure in Humans
McCarthy, B., Henderson, L. A., & Macefield, V. G. (2023) · Comprehensive physiology · doi:10.1002/cphy.c220021 · Cited by 8
Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies
Gan, D., Qin, L., & Xiao, G. (2026) · Research · doi:10.34133/research.1319 · Cited by 1
“Selectively blocking sympathetic β -adrenergic signaling, inhibiting TRP channels activated by lipotoxic metabolites, or enhancing osteoanabolic signaling derived from sensory nerves could restore osteoblast–osteoclast coupling [ 89 , 90 ].”

Authors: Elefteriou, F., Ahn, J. D., Takeda, S., Starbuck, M., Yang, X., Liu, X., Kondo, H., Richards, W. G., Bannon, T. W., Noda, M., Clement, K., Vaisse, C., & Karsenty, G.
Affiliations: Baylor College of Medicine (US)
Tokyo Medical and Dental University (JP)
Amgen (United States) (US)
University of California, San Francisco (US)
ORCID: Elefteriou, Florent
Yang, Xiangli
Liu, Xiuyun
Kondo, Hisataka
Richards, William G.
Noda, Masaki
Vaisse, Christian
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-02-20
Volume: 434
Issue: 7032
Pages: 514-520
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature03398
OpenAlex: W1997508587
Cited by: 1,311
References: 17
Citations by year: 2026: 45 · 2025: 46 · 2024: 55 · 2023: 43 · 2022: 38 · 2021: 59 · 2020: 51 · 2019: 48 · 2018: 51 · 2017: 52 · 2016: 53 · 2015: 69 · 2014: 83 · 2013: 67 · 2012: 84
FWCI: 30.49
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R01DK060540)
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 resorption, bone remodeling, sympathetic nervous system, osteoclastogenesis, RANKL, beta2-adrenergic receptor, protein kinase A, osteoblasts, gonadectomy, osteoporosis, ob/ob mice, gonadal failure
MeSH terms: Cocaine- and Amphetamine-Regulated Transcript Protein, Amino Acid Sequence, Animals, Bone Resorption, Carrier Proteins, Cell Line, Child, Child, Preschool, Humans, Male, Membrane Glycoproteins, Models, Neurological, Neoplasm Proteins, Nerve Tissue Proteins, Osteoblasts, Osteogenesis, Sympathetic Nervous System, Transcription Factors, Signal Transduction, Gene Deletion, Cyclic AMP-Dependent Protein Kinases, Receptors, Adrenergic, beta-2, Response Elements, Leptin, Receptor, Melanocortin, Type 4, Mice, Activating Transcription Factor 4, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, 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

Leptin regulation of bone resorption by the sympathetic nervous system and CART

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks