ArticleThe EMBO journal2023
A Zeb1/MtCK1 metabolic axis controls osteoclast activation and skeletal remodeling.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Extracellular vesicle-mediated crosstalk in bone: miR-150-5p as a mechanosensitive regulator of osteoclastogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- ZEB1 drives terminal erythroid maturation by controlling the GATA2-KLF1 regulatory switch.Nucleic acids research · 2026Article
- ZEB1 maintains mitochondrial fission and macrophage efferocytosis by restraining MFN2, thereby limiting inflammation and improving tendon‑bone healing.International journal of molecular medicine · 2026Article
- Article
- Ex Vivo Osteoclastogenesis from Peripheral Blood Mononuclear Cells Is Unchanged in Adults with Phenylketonuria, Regardless of Dietary Compliance.International journal of molecular sciences · 2025Article
- Epithelial-to-mesenchymal transition transcription factors: New strategies for mesenchymal tissue regeneration.Cytokine & growth factor reviews · 2025Review
- MTHFD2 promotes osteoclastogenesis and bone loss in rheumatoid arthritis by enhancing CKMT1-mediated oxidative phosphorylation.BMC medicine · 2025Article
- ZEB1 expression in Th17 cells correlated with p-STAT3 in human apical periodontitis.BMC oral health · 2025Article
- An In Vitro Model of Murine Osteoclast-Mediated Bone Resorption.Bio-protocol · 2024Article
- PRMT6 Epigenetically Drives Metabolic Switch from Fatty Acid Oxidation toward Glycolysis and Promotes Osteoclast Differentiation During Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Single-cell RNA sequencing reveals the cellular and molecular heterogeneity of treatment-naïve primary osteosarcoma in dogs.Communications biology · 2024Article
- Association between Metabolic Syndrome and Musculoskeletal Status: A Cross-Sectional Study of NHANES.International journal of endocrinology · 2024Article
- Mitochondrial ATP concentration decreases immediately after glucose administration to glucose-deprived hepatocytes.FEBS open bio · 2024Article
- A Zeb1/MtCK1 metabolic axis controls osteoclast activation and skeletal remodeling.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Osteoclasts are bone-resorbing polykaryons responsible for skeletal remodeling during health and disease. Coincident with their differentiation from myeloid precursors, osteoclasts undergo extensive transcriptional and metabolic reprogramming in order to acquire the cellular machinery necessary to demineralize bone and digest its interwoven extracellular matrix. While attempting to identify new regulatory molecules critical to bone resorption, we discovered that murine and human osteoclast differentiation is accompanied by the expression of Zeb1, a zinc-finger transcriptional repressor whose role in normal development is most frequently linked to the control of epithelial-mesenchymal programs. However, following targeting, we find that Zeb1 serves as an unexpected regulator of osteoclast energy metabolism. In vivo, Zeb1-null osteoclasts assume a hyperactivated state, markedly decreasing bone density due to excessive resorptive activity. Mechanistically, Zeb1 acts in a rheostat-like fashion to modulate murine and human osteoclast activity by transcriptionally repressing an ATP-buffering enzyme, mitochondrial creatine kinase 1 (MtCK1), thereby controlling the phosphocreatine energy shuttle and mitochondrial respiration. Together, these studies identify a novel Zeb1/MtCK1 axis that exerts metabolic control over bone resorption in vitro and in vivo.
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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.