ArticlePLoS genetics2015
mTORC1 Prevents Preosteoblast Differentiation through the Notch Signaling Pathway.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 99 citations in OpenAlex.
- Reprogramming bone homeostasis: The recoupling-oriented framework of bidirectional regulation strategies for osteoporosis.iScience · 2026Review
- mTOR signalling mediates the spinal osteoblast pathotype at the curve apex in adolescent idiopathic scoliosis.Scientific reports · 2026Article
- Region- and Compartment-Specific Elevation of Bone Mass in Mice Following Tsc1 Deletion in 8-kb Dmp1-Cre-Expressing Cells.Calcified tissue international · 2026Article
- Soluble Sema4D From γδ T Cells Exerts Osteoblast Inhibition via Plexin-B/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws.Cell proliferation · 2026Article
- Loss of Tsc1 in Osterix-expressing cells leads to greater bone mass and strength in mice.Bone · 2026Article
- Stage-dependent endoplasmic reticulum homeostasis in osteogenic differentiation.Frontiers in cell and developmental biology · 2026Review
- Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments.Clinical and translational medicine · 2025Review
- Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling.Bone research · 2025Review
- Psoralen-mediated regulation of osteogenic differentiation of periodontal ligament stem cells: involvement of the mTOR pathway.Frontiers in cell and developmental biology · 2025Article
- Naked cuticle homolog 2 controls the differentiation of osteoblasts and osteoclasts and ameliorates bone loss in ovariectomized mice.Genes & diseases · 2025Article
- Bitter acids from Humulus lupulus L. alleviate D-galactose induced osteoblastic senescence and bone loss via regulating AKT/mTOR-mediated autophagy.Journal of food and drug analysis · 2024Article
- Rapamycin Inhibits Senescence and Improves Immunomodulatory Function of Mesenchymal Stem Cells Through IL-8 and TGF-β Signaling.Stem cell reviews and reports · 2024Article
- Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice.JBMR plus · 2024Article
- Odontoblasts release exosomes to regulate the odontoblastic differentiation of dental pulp stem cells.Stem cell research & therapy · 2023Article
- Article
- PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action.Frontiers in pharmacology · 2023Review
- Contrasting effects ofeLife · 2022Article
- The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis.Cell communication and signaling : CCS · 2022Review
- Cell energy metabolism and bone formation.Bone reports · 2022Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic target of rapamycin (mTOR) integrates both intracellular and extracellular signals to regulate cell growth and metabolism. However, the role of mTOR signaling in osteoblast differentiation and bone formation is undefined, and the underlying mechanisms have not been elucidated. Here, we report that activation of mTOR complex 1 (mTORC1) is required for preosteoblast proliferation; however, inactivation of mTORC1 is essential for their differentiation and maturation. Inhibition of mTORC1 prevented preosteoblast proliferation, but enhanced their differentiation in vitro and in mice. Activation of mTORC1 by deletion of tuberous sclerosis 1 (Tsc1) in preosteoblasts produced immature woven bone in mice due to excess proliferation but impaired differentiation and maturation of the cells. The mTORC1-specific inhibitor, rapamycin, restored these in vitro and in vivo phenotypic changes. Mechanistically, mTORC1 prevented osteoblast maturation through activation of the STAT3/p63/Jagged/Notch pathway and downregulation of Runx2. Preosteoblasts with hyperactive mTORC1 reacquired the capacity to fully differentiate and maturate when subjected to inhibition of the Notch pathway. Together, these findings identified the role of mTORC1 in osteoblast formation and established that mTORC1 prevents preosteoblast differentiation and maturation through activation of the Notch pathway.
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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.