ArticleNature medicine2008
Dimorphic effects of Notch signaling in bone homeostasis.
Article in Nature medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
228 citing papers in PubMed, 2 syntheses or guidelines pooled it, 417 citations in OpenAlex.
- Insights into the mechanism of vascular endothelial cells on bone biology.Bioscience reports · 2021Pooled it
- Hajdu-Cheney Syndrome: A Systematic Review of the Literature.International journal of environmental research and public health · 2020Pooled it
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Myeloid-Specific Deletion ofBiomedicines · 2026Article
- Reduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model.JCI insight · 2026Article
- Role of Notch signaling in corticalization.Journal of endocrinological investigation · 2026Review
- Article
- Engineered Dll4-overexpressing osteocyte-derived exosomes enhanced bone regeneration by regulating osteogenesis and angiogenesis.Theranostics · 2026Article
- Brushite-modified titanium surface elicits early osteointegrative gene expression signatures in human mesenchymal stem cells: insights from NGS analysis.Frontiers in bioengineering and biotechnology · 2026Article
- Role of Notch signaling pathway in joint homeostasis and osteoarthritis.Frontiers in bioengineering and biotechnology · 2026Review
- The Notch signaling pathway in regulating bone and cartilage homeostasis: novel insights into the pathogenesis and therapeutics of osteoarthritis.Cell communication and signaling : CCS · 2025Review
- Brain-Bone Axis in Physiological and Pathological Conditions.International journal of molecular sciences · 2025Review
- Engineered bone-targeting apoptotic vesicles as a minimally invasive nanotherapy for heterotopic ossification.Journal of nanobiotechnology · 2025Article
- Biomimetic Microstructured Scaffold with Release of Re-Modified Teriparatide for Osteoporotic Tendon-to-Bone Regeneration via Balancing Bone Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Orphan nuclear receptor NR4A1 regulates both osteoblastogenesis and adipogenesis in human mesenchymal stem cells.Molecular medicine reports · 2025Article
- Metabolic reprogramming in skeletal cell differentiation.Bone research · 2024Review
- Nanofiber-induced hierarchically-porous magnesium phosphate bone cements accelerate bone regeneration by inhibiting Notch signaling.Bioactive materials · 2024Article
- Endothelial to mesenchymal Notch signaling regulates skeletal repair.JCI insight · 2024Article
- A homozygousJBMR plus · 2024Article
168 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Notch signaling is a key mechanism in the control of embryogenesis. However, its in vivo function during mesenchymal cell differentiation, and, specifically, in bone homeostasis, remains largely unknown. Here, we show that osteoblast-specific gain of Notch function causes severe osteosclerosis owing to increased proliferation of immature osteoblasts. Under these pathological conditions, Notch stimulates early osteoblastic proliferation by upregulating the genes encoding cyclin D, cyclin E and Sp7 (osterix). The intracellular domain of Notch1 also regulates terminal osteoblastic differentiation by directly binding Runx2 and repressing its transactivation function. In contrast, loss of all Notch signaling in osteoblasts, generated by deletion of the genes encoding presenilin-1 and presenilin-2 in bone, is associated with late-onset, age-related osteoporosis, which in turn results from increased osteoblast-dependent osteoclastic activity due to decreased osteoprotegerin mRNA expression in these cells. Together, these findings highlight the potential dimorphic effects of Notch signaling in bone homeostasis and may provide direction for novel therapeutic applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.