The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation
Open accessAbstract
Postnatal bone marrow houses mesenchymal progenitor cells that are osteoblast precursors. These cells have established therapeutic potential, but they are difficult to maintain and expand in vitro, presumably because little is known about the mechanisms controlling their fate decisions. To investigate the potential role of Notch signaling in osteoblastogenesis, we used conditional alleles to genetically remove components of the Notch signaling system during skeletal development. We found that disruption of Notch signaling in the limb skeletogenic mesenchyme markedly increased trabecular bone mass in adolescent mice. Notably, mesenchymal progenitors were undetectable in the bone marrow of mice with high bone mass. As a result, these mice developed severe osteopenia as they aged. Moreover, Notch signaling seemed to inhibit osteoblast differentiation through Hes or Hey proteins, which diminished Runx2 transcriptional activity via physical interaction. These results support a model wherein Notch signaling in bone marrow normally acts to maintain a pool of mesenchymal progenitors by suppressing osteoblast differentiation. Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway.
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
“According to pharmacological and molecular biology studies, Notch signaling is crucial in differentiating mesenchymal stem cells into osteoblasts [35].”
From Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review (2025) · cites this paper as [35]
Citations
Cites
Notch Signaling: Cell Fate Control and Signal Integration in Development
Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999) · Science · doi:10.1126/science.284.5415.770 · Cited by 5,909
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications
Bianco, P., Riminucci, M., Gronthos, S., & Robey, P. G. (2001) · Stem Cells · doi:10.1634/stemcells.19-3-180 · Cited by 1,944
Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain
Schroeter, E. H., Kisslinger, J. A., & Kopan, R. (1998) · Nature · doi:10.1038/30756 · Cited by 1,624
Self-citationReaching a Genetic and Molecular Understanding of Skeletal Development
Karsenty, G., & Wagner, E. F. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00157-0 · Cited by 1,611
Mutations in NOTCH1 cause aortic valve disease
Garg, V., Muth, A. N., Ransom, J. F., Schluterman, M. K., Barnes, R., King, I. N., Grossfeld, P. D., & Srivastava, D. (2005) · Nature · doi:10.1038/nature03940 · Cited by 1,509
HES and HERP families: Multiple effectors of the notch signaling pathway
Iso, T., Kedes, L., & Hamamori, Y. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10208 · Cited by 1,259
Stromal Stem Cells: Marrow‐Derived Osteogenic Precursors
Owen, M. E., & Friedenstein, A. J. (2007) · Novartis Foundation symposium · doi:10.1002/9780470513637.ch4 · Cited by 1,225
Notch signaling is essential for vascular morphogenesis in micePreprint
Krebs, L. T., Xue, Y., Norton, C. R., Shutter, J. R., Maguire, M., Sundberg, J. P., Gallahan, D., Closson, V., Kitajewski, J., Callahan, R., et al. (2000) · Genes & Development · doi:10.1101/gad.14.11.1343 · Cited by 1,065
Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer
Logan, M., Martin, J. F., Nagy, A., Lobe, C., Olson, E., & Tabin, C. (2002) · Genesis · doi:10.1002/gene.10092 · Cited by 1,022
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of bone development and repair
Salhotra, A., Shah, H. N., Lévi, B., & Longaker, M. T. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00279-w · Cited by 1,302
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
Self-citationNotch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,216
Endothelial Notch activity promotes angiogenesis and osteogenesis in bone
Ramasamy, S. K., Kusumbe, A. P., Wang, L., & Adams, R. H. (2014) · Nature · doi:10.1038/nature13146 · Cited by 1,071
Bone biomaterials and interactions with stem cells
Gao, C., Peng, S., Feng, P., & Shuai, C. (2017) · Bone Research · doi:10.1038/boneres.2017.59 · Cited by 748
Metadata
- Authors
- Hilton, M. J., Tu, X., Wu, X., Bai, S., Zhao, H., Kobayashi, T., Kronenberg, H. M., Teitelbaum, S. L., Ross, F. P., Kopan, R., & Long, F.
- Affiliations
- Washington University in St. Louis (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Long, Fanxin
- ORCID
- Venue
- Nature Medicine
- Published
- 2008-02-24
- Volume
- 14
- Issue
- 3
- Pages
- 306-314
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC2740725
- OpenAlex
- W2050599075
- Cited by
- 604
- References
- 48
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 20 · 2023: 25 · 2022: 21 · 2021: 37 · 2020: 37 · 2019: 33 · 2018: 36 · 2017: 41 · 2016: 41 · 2015: 43 · 2014: 42 · 2013: 40 · 2012: 38
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK065789, DK11794, P01DK011794, R01DK065789)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 046852, 5 T32 AR07033, R37AR046523, AR046523, T32AR007033, R01AR046852, R01AR046523)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 044056, R01HD044056)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- Notch signaling, osteogenic differentiation, osteoblastogenesis, Runx2, trabecular bone mass, osteopenia, skeletal development, limb mesenchyme
- MeSH terms
- Aging, Animals, Bone Development, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Mutation, Osteoblasts, Phenotype, Signal Transduction, Gene Deletion, Mice, Receptors, Notch, Amyloid Precursor Protein Secretases, Mesenchymal Stem Cells
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
