ArticleAmerican journal of physiology. Endocrinology and metabolism2016
Canonical Notch activation in osteocytes causes osteopetrosis.
Article in American journal of physiology. Endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Notch Signalling Pathway in the Pathogenesis of Periodontitis: Research Progress.International dental journal · 2026Review
- Osteocyte Cell-Cell Communication Within and Beyond Bone.Current osteoporosis reports · 2026Review
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Review
- Targeting osteocytes vs osteoblasts.Bone · 2023Review
- Non-canonical Wnt signaling participates in Jagged1-induced osteo/odontogenic differentiation in human dental pulp stem cells.Scientific reports · 2022Article
- Notch2 Blockade Mitigates Methotrexate Chemotherapy-Induced Bone Loss and Marrow Adiposity.Cells · 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
- Impact of the host response and osteoblast lineage cells on periodontal disease.Frontiers in immunology · 2022Review
- The osteocyte as a signaling cell.Physiological reviews · 2022Review
- Transcriptomic analysis provides a new insight: Oleuropein reverses high glucose-induced osteogenic inhibition in bone marrow mesenchymal stem cellsFrontiers in bioengineering and biotechnology · 2022Article
- Inhibition of Notch Signaling Stimulates Osteoclastogenesis From the Common Trilineage Progenitor Under Inflammatory Conditions.Frontiers in immunology · 2022Article
- Review
- The interaction of Notch and Wnt signaling pathways in vertebrate regeneration.Cell regeneration (London, England) · 2021Review
- The multifunctional role of Notch signaling in multiple myeloma.Journal of cancer metastasis and treatment · 2021Article
- Review
- Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis.Biomolecules · 2020Review
- Notch Signaling in Osteogenesis, Osteoclastogenesis, and Angiogenesis.The American journal of pathology · 2019Review
- Contextual Regulation of Skeletal Physiology by Notch Signaling.Current osteoporosis reports · 2019Review
- Overexpression of Notch Signaling Induces Hyperosteogeny in Zebrafish.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Activation of Notch1 in cells of the osteoblastic lineage inhibits osteoblast differentiation/function and causes osteopenia, whereas its activation in osteocytes causes a distinct osteopetrotic phenotype. To explore mechanisms responsible, we established the contributions of canonical Notch signaling (Rbpjκ dependent) to osteocyte function. Transgenics expressing Cre recombinase under the control of the dentin matrix protein-1 (Dmp1) promoter were crossed with Rbpjκ conditional mice to generate Dmp1-Cre(+/-);Rbpjκ(Δ/Δ) mice. These mice did not have a skeletal phenotype, indicating that Rbpjκ is dispensable for osteocyte function. To study the Rbpjκ contribution to Notch activation, Rosa(Notch) mice, where a loxP-flanked STOP cassette is placed between the Rosa26 promoter and the NICD coding sequence, were crossed with Dmp1-Cre transgenic mice and studied in the context (Dmp1-Cre(+/-);Rosa(Notch);Rbpjκ(Δ/Δ)) or not (Dmp1-Cre(+/-);Rosa(Notch)) of Rbpjκ inactivation. Dmp1-Cre(+/-);Rosa(Notch) mice exhibited increased femoral trabecular bone volume and decreased osteoclasts and bone resorption. The phenotype was reversed in the context of the Rbpjκ inactivation, demonstrating that Notch canonical signaling was accountable for the phenotype. Notch activation downregulated Sost and Dkk1 and upregulated Axin2, Tnfrsf11b, and Tnfsf11 mRNA expression, and these effects were not observed in the context of the Rbpjκ inactivation. In conclusion, Notch activation in osteocytes suppresses bone resorption and increases bone volume by utilization of canonical signals that also result in the inhibition of Sost and Dkk1 and upregulation of Wnt signaling.
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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.