ArticleProceedings of the National Academy of Sciences of the United States of America2016
Anabolic actions of Notch on mature bone.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- Synergistic Crosstalk of PACAP and Notch Signaling Pathways in Bone Development.International journal of molecular sciences · 2025Article
- Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players.Stem cell research & therapy · 2025Review
- Integrated transcriptomic analysis of human induced pluripotent stem cell-derived osteogenic differentiation reveals a regulatory role of KLF16.bioRxiv : the preprint server for biology · 2025Article
- Alendronate partially rescues the periodontal defects in OIM mouse model of osteogenesis imperfecta.Scientific reports · 2025Article
- Lipid metabolism and osteonecrosis: unraveling causal mechanisms via multi-omics and mendelian randomization.Frontiers in physiology · 2025Article
- Targeted Overexpression ofBiology · 2024Article
- Cellular senescence in skeletal disease: mechanisms and treatment.Cellular & molecular biology letters · 2023Review
- Loss of Notch signaling in skeletal stem cells enhances bone formation with aging.Bone research · 2023Article
- Proteomic Analysis of Female Synovial Fluid to Identify Novel Biomarkers for Osteoarthritis.Life (Basel, Switzerland) · 2023Article
- Article
- Inflammatory macrophages interrupt osteocyte maturation and mineralization via regulating the Notch signaling pathway.Molecular medicine (Cambridge, Mass.) · 2022Article
- Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration.Science advances · 2022Article
- The Notch pathway regulates the bone gain induced by PTH anabolic signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Signaling network regulating osteogenesis in mesenchymal stem cells.Journal of cell communication and signaling · 2022Review
- Article
- The osteocyte as a signaling cell.Physiological reviews · 2022Review
- The interaction of Notch and Wnt signaling pathways in vertebrate regeneration.Cell regeneration (London, England) · 2021Review
- Relevance of Notch Signaling for Bone Metabolism and Regeneration.International journal of molecular sciences · 2021Review
- Osteocytes but not osteoblasts directly build mineralized bone structures.International journal of biological sciences · 2021Article
- The multifunctional role of Notch signaling in multiple myeloma.Journal of cancer metastasis and treatment · 2021Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Notch controls skeletogenesis, but its role in the remodeling of adult bone remains conflicting. In mature mice, the skeleton can become osteopenic or osteosclerotic depending on the time point at which Notch is activated or inactivated. Using adult EGFP reporter mice, we find that Notch expression is localized to osteocytes embedded within bone matrix. Conditional activation of Notch signaling in osteocytes triggers profound bone formation, mainly due to increased mineralization, which rescues both age-associated and ovariectomy-induced bone loss and promotes bone healing following osteotomy. In parallel, mice rendered haploinsufficient in γ-secretase presenilin-1 (Psen1), which inhibits downstream Notch activation, display almost-absent terminal osteoblast differentiation. Consistent with this finding, pharmacologic or genetic disruption of Notch or its ligand Jagged1 inhibits mineralization. We suggest that stimulation of Notch signaling in osteocytes initiates a profound, therapeutically relevant, anabolic response.
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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.