ArticleCell death & disease2018
A novel phosphorylation by AMP-activated kinase regulates RUNX2 from ubiquitination in osteogenesis over adipogenesis.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 65 citations in OpenAlex.
- The Role of Runx2 in Microtubule Dynamics and Its Effects on Osteoblast Migration.Cytoskeleton (Hoboken, N.J.) · 2026Article
- Repurposing Metformin to Promote Fracture Callus Maturation via AMPK-Driven Metabolic Activation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Bioinspired, Mitochondria-Targeted Single-Atom Nanozyme Enhances Bone Regeneration by Reprogramming Stem Cell Energy Metabolism.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dose-Dependent Impact of Metformin on Osteoblast-Specific Biomarkers in Cultured Rat Primary Osteoblasts.Physiological research · 2026Article
- AMPK/mTORC2/AKT-473/RUNX2 signaling axis modulates epithelial-mesenchymal transition and bone tropism in breast cancer.Frontiers in oncology · 2026Article
- Metformin reverses periodontal destruction caused by experimental periodontitis by inhibiting interleukin-1β activity.Journal of periodontology · 2025Article
- Understanding proneural-mesenchymal transition using patient-derived glioma stem-like cell (GSC) organoids and engineered extracellular matrix.bioRxiv : the preprint server for biology · 2025Article
- Molecular Crosstalk Between RUNX2 and HIF-1α in Osteosarcoma: Implications for Angiogenesis, Metastasis, and Therapy Resistance.International journal of molecular sciences · 2025Review
- Metabotissugenic citrate biomaterials orchestrate bone regeneration via citrate-mediated signaling pathways.Science advances · 2025Article
- AMP-activated protein kinase (AMPK) is essential for tendon homeostasis and prevents premature senescence and ectopic calcification.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial Transplantation: A Paradigm Shift in Osteoporosis Therapy.International journal of nanomedicine · 2025Review
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Autophagy: regulating the seesaw of bone-fat balance.Frontiers in cell and developmental biology · 2025Review
- Osteoprotegerin mediates adipogenesis in obesity.Journal of advanced research · 2024Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Association of Body Mass Index and Chronology of Tooth Eruption in Children visiting a Dental Hospital in UAE: A Cross-sectional Study.The Saudi dental journal · 2024Article
- WWP1 E3 ligase at the crossroads of health and disease.Cell death & disease · 2023Review
- AMPK-induced novel phosphorylation of RUNX1 inhibits STAT3 activation and overcome imatinib resistance in chronic myelogenous leukemia (CML) subjects.Cell death discovery · 2023Article
- Phosphorylated MAPK11 promotes the progression of clear cell renal cell carcinoma by maintaining RUNX2 protein abundance.Journal of cellular and molecular medicine · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) function as progenitors to a variety of cell types. The reported association between osteogenic and adipogenic commitment during differentiation is due to the regulation of key transcription factors in the signaling pathways. However, the process of adipogenesis at the expense of osteogenic phenotype during metabolic stress is still unclear. In this study, we showed for the first time that RUNX2 is a novel substrate of AMP-activated kinase (AMPK), which directly phosphorylates at serine 118 residue in the DNA-binding domain of RUNX2. Our results in in vitro MSC lineage differentiation models confirmed that active AMPK and RUNX2-S118 phosphorylation are preferentially associated with osteogenic commitment, whereas the lack of this phosphorylation leads to adipogenesis. This interplay is regulated by the ubiquitination of non-phosphorylated RUNX2-S118, which is evident in the dominant mutant RUNX2-S118D. Pharmacological activation of AMPK by metformin significantly abrogated the loss of RUNX2-S118 phosphorylation and protected from tunicamycin-induced endoplasmic reticulum stress, high glucose-induced in vitro adipogenesis and streptozotocin-induced in vivo bone adiposity and bone phenotype. In conclusion, results from this study demonstrated that RUNX2 is a direct target of AMPK which simplified the outlook towards several complex mechanisms that are currently established concerning cellular metabolism and pathogenesis.
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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.