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
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…
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
“A polymorphism of the first intron of the gene coding for the type I collagen α1 chain and increased levels of homocysteine can influence fracture risk independent of BMD”
From Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005) · cites this paper as [101]
Citations
Cites
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-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-citationGenetic 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-citationTwo 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
Cited by
Sorted by citations
The integrated stress response
Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659
“Phosphorylation of ATF4 at S245 by ribosomal protein S6 kinase a -2 (RSK2) or S254 by protein kinase A (PKA) can enhance its transcriptional activity during osteoblast and osteoclast differentiation [107,159].”
Pathogenesis of osteoporosis: concepts, conflicts, and prospects
Raisz, L. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27071 · Cited by 1,779
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
Haematopoietic stem cell release is regulated by circadian oscillations
Méndez‐Ferrer, S., Lucas, D., Battista, M., & Frenette, P. S. (2008) · Nature · doi:10.1038/nature06685 · Cited by 1,310
Building strong bones: molecular regulation of the osteoblast lineage
Long, F. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3254 · Cited by 1,211
“First, it directly regulates the expression of the osteoblast-derived molecules osteocalcin (a bone matrix protein with newly reported roles in glucose homeostasis and male fertility ( Box 1 )) and receptor activator of nuclear factor-κB ligand (RANKL; also known as TNFSF11), which promotes osteoclast differentiation…”
Metadata
- 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
- Venue
- Nature
- Published
- 2005-02-20
- Volume
- 434
- Issue
- 7032
- Pages
- 514-520
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
