ArticleCell death discovery2022
High glutamine suppresses osteogenesis through mTORC1-mediated inhibition of the mTORC2/AKT-473/RUNX2 axis.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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.
The trial behind it
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Branched‑chain amino acid metabolism and bone metabolism: Implications for osteoporosis pathogenesis and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Bone marrow mesenchymal stromal cells metabolic reprogramming in systemic lupus erythematosus: remodeling of bone marrow microenvironment and regulation of immune cell fate.Frontiers in immunology · 2026Review
- AMPK/mTORC2/AKT-473/RUNX2 signaling axis modulates epithelial-mesenchymal transition and bone tropism in breast cancer.Frontiers in oncology · 2026Article
- Article
- Metabolic markers detect early ostedifferentiation of mesenchymal stem cells from multiple donors.Stem cell research & therapy · 2025Article
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- From molecular mechanism to plant intervention: the bidirectional regulation of inflammation and oxidative stress in bone aging.Frontiers in endocrinology · 2025Review
- The microbial metabolite imidazole propionate dysregulates bone homeostasis by inhibiting AMP-activated protein kinase (AMPK) signaling.Communications biology · 2024Article
- Plasmacytoid Dendritic Cells Mediate CpG-ODN-induced Increase in Survival in a Mouse Model of Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2024Article
- mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.International journal of molecular sciences · 2024Review
- Plasmacytoid dendritic cells mediate CpG-ODN induced increase in survival in a mouse model of lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- 2P-FLIM unveils time-dependent metabolic shifts during osteogenic differentiation with a key role of lactate to fuel osteogenesis via glutaminolysis identified.Stem cell research & therapy · 2023Article
- AMPK-induced novel phosphorylation of RUNX1 inhibits STAT3 activation and overcome imatinib resistance in chronic myelogenous leukemia (CML) subjects.Cell death discovery · 2023Article
- Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH).Molecular biology reports · 2023Article
- mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.International journal of molecular sciences · 2023Review
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of the key nutrient cellular sensors mTORC1 and mTORC2 directs the fate of mesenchymal stromal cells (MSCs). Here, we report that glutamine regulates crosstalk between mTOR complexes and lineage commitment of MSCs independent of glucose concentration. High glutamine-induced mTORC1 hyperactivation resulted in the suppression of mTORC2, which otherwise stabilizes RUNX2 via GSK3β inhibition through pAKT-473. Activation of GSK3β resulted in the ubiquitination of RUNX2, a key transcription factor for the osteogenic commitment of MSCs. However, low glutamine conditions inhibit mTORC1 hyperactivation followed by increased mTORC2 activation and RUNX2 stabilization. Under diabetic/high-glucose conditions, glutamine-triggered hyperactivation of mTORC1 resulted in mTORC2 suppression, and active GSK3β led to suppression of RUNX2. Activation of p-AMPK by metformin inhibits high glutamine-induced mTORC1 hyperactivation and rescues RUNX2 through the mTORC2/AKT-473 axis. Collectively, our study indicates the role of glutamine in modulating MSC fate through cross-talk between mTOR complexes by identifying a critical switch in signaling. It also shows the importance of glutamine in modulating molecular cues (mTORC1/p-70S6K/mTORC2/RUNX2) that are involved in driving diabetes-induced bone adipogenesis and other secondary complications.
Identifiers
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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.