ArticleThe Journal of clinical investigation2018
Notch signaling suppresses glucose metabolism in mesenchymal progenitors to restrict osteoblast differentiation.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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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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Who cites it
74 citing papers in PubMed, 105 citations in OpenAlex.
- Modelling 16/8 intermittent fasting and breakfast-skipping in mouse adipocytes 3T3-L1 in vitro: a transcriptomics study.Journal, genetic engineering & biotechnology · 2026Article
- Myeloid-Specific Deletion ofBiomedicines · 2026Article
- Pathophysiology and Molecular Signalling in Osteoporosis: Linking Risk Factors to Bone Loss.Journal of cellular and molecular medicine · 2026Review
- Hyperglycemia Leads to BMSC Impaired Osteogenesis, Enhanced Adipogenesis, and Altered Metabolism.Journal of cellular biochemistry · 2026Article
- Dual Osteoprotective Actions of the Kefir Peptide KFP-1: Enhancement of Bone Formation and Suppression of Bone Resorption in Cells and Murine Models.Calcified tissue international · 2026Article
- Bone Marrow Mesenchymal Stromal Cell Osteogenesis is driven by Paracrine signals from Regulatory T Cell.Stem cell reviews and reports · 2026Article
- MicroRNA-127-3p Inhibits In Vitro Osteogenesis and Dampens Trauma-Induced Heterotopic Ossification In Vivo.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- 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
- Maternal group BAnnals of medicine · 2025Article
- miR-34c-5p targets Notch2 to promote fracture healing.Journal of orthopaedic surgery and research · 2025Article
- PLAGL1-IGF2 axis regulates osteogenesis of postnatal condyle development.International journal of oral science · 2025Article
- Impact of Acute Myeloid Leukemia Cells on the Metabolic Function of Bone Marrow Mesenchymal Stem Cells.International journal of molecular sciences · 2025Article
- Overexpression ofTranslational lung cancer research · 2025Article
- NOTCH Signaling Networks in Perivascular Adipose Tissue.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- The inhibition of PINK1/Drp1-mediated mitophagy by hyperglycemia leads to impaired osteoblastogenesis in diabetes.iScience · 2025Article
- Spatiotemporal application of small molecules in fracture healing.Biomaterials translational · 2025Review
- The Role of Sirtuins in Bone Repair From the Perspective of Glucose Metabolism.International journal of general medicine · 2025Review
- Notch2 Signaling Drives Cardiac Hypertrophy by Suppressing Purine Nucleotide Metabolism.Research (Washington, D.C.) · 2025Article
- NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.Nature communications · 2024Article
- Metabolic reprogramming in skeletal cell differentiation.Bone research · 2024Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Notch signaling critically controls cell fate decisions in mammals, both during embryogenesis and in adults. In the skeleton, Notch suppresses osteoblast differentiation and sustains bone marrow mesenchymal progenitors during postnatal life. Stabilizing mutations of Notch2 cause Hajdu-Cheney syndrome, which is characterized by early-onset osteoporosis in humans, but the mechanism whereby Notch inhibits bone accretion is not fully understood. Here, we report that activation of Notch signaling by either Jagged1 or the Notch2 intracellular domain suppresses glucose metabolism and osteoblast differentiation in primary cultures of bone marrow mesenchymal progenitors. Importantly, deletion of Notch2 in the limb mesenchyme increases both glycolysis and bone formation in the long bones of postnatal mice, whereas pharmacological reduction of glycolysis abrogates excessive bone formation. Mechanistically, Notch reduces the expression of glycolytic and mitochondrial complex I genes, resulting in a decrease in mitochondrial respiration, superoxide production, and AMPK activity. Forced activation of AMPK restores glycolysis in the face of Notch signaling. Thus, suppression of glucose metabolism contributes to the mechanism, whereby Notch restricts osteoblastogenesis from bone marrow mesenchymal progenitors.
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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.