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.
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“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]
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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
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