ArticleThe Journal of clinical investigation2018
Vhl deletion in osteoblasts boosts cellular glycolysis and improves global glucose metabolism.
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 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Can Hypoxic Conditioning Improve Bone Metabolism? A Systematic Review.International journal of environmental research and public health · 2019Pooled it
- Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation.The Journal of clinical investigation · 2021Trial
- Regulating Glucose Metabolism Enzymes for Osteoporosis Therapy: Current and Future Approaches.International journal of molecular sciences · 2026Review
- Article
- Dynamic microenvironments for bone organoids: spatiotemporal regulation of angiogenic-osteogenic coupling through advanced hydrogel design.Frontiers in bioengineering and biotechnology · 2026Review
- Regional and Sexual Dimorphism in Murine Skeletal Responses to Osteocytic HIF Pathway Modulation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Maternal group BAnnals of medicine · 2025Article
- The role of bone in whole-body energy metabolism.Nature reviews. Endocrinology · 2025Review
- Developmental low-dose bisphenol A exposure leads to extensive transcriptome female masculinization and male feminization later in life.Communications medicine · 2025Article
- An "inside-out"-guided genetically engineered hydrogel for augmenting aged bone regeneration.Bioactive materials · 2025Article
- Chronic intermittent hypoxia impairs BM-MSC osteogenesis and long bone growth through regulating histone lactylation.Journal of translational medicine · 2025Article
- High Dietary Phosphorus Impairs Bone Microarchitecture and Induces Alterations in the LGR4-R-Spondins Axis in Rats with Normal Renal Function.Nutrients · 2025Article
- N6-Methyladenosine Modification of the Three Components "Writers", "Erasers", and "Readers" in Relation to Osteogenesis.International journal of molecular sciences · 2025Review
- Skeletal stem and progenitor cells in bone physiology, ageing and disease.Nature reviews. Endocrinology · 2025Review
- Wnt7b overexpression in osteoblasts stimulates bone formation and reduces obesity in mice on a high-fat diet.JBMR plus · 2024Article
- Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity.Nature communications · 2024Article
- Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.Journal of clinical medicine · 2024Article
- Metabolic regulation of skeletal cell fate and function.Nature reviews. Endocrinology · 2024Review
- Activation of the osteoblastic HIF-1α pathway partially alleviates the symptoms of STZ-induced type 1 diabetes mellitus via RegIIIγ.Experimental & molecular medicine · 2024Article
- The skeleton: an overlooked regulator of systemic glucose metabolism in cancer?Frontiers in oncology · 2024Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
The skeleton has emerged as an important regulator of systemic glucose homeostasis, with osteocalcin and insulin representing prime mediators of the interplay between bone and energy metabolism. However, genetic evidence indicates that osteoblasts can influence global energy metabolism through additional, as yet unknown, mechanisms. Here, we report that constitutive or postnatally induced deletion of the hypoxia signaling pathway component von Hippel-Lindau (VHL) in skeletal osteolineage cells of mice led to high bone mass as well as hypoglycemia and increased glucose tolerance, not accounted for by osteocalcin or insulin. In vitro and in vivo data indicated that Vhl-deficient osteoblasts displayed massively increased glucose uptake and glycolysis associated with upregulated HIF-target gene expression, resembling the Warburg effect that typifies cancer cells. Overall, the glucose consumption by the skeleton was increased in the mutant mice, as revealed by 18F-FDG radioactive tracer experiments. Moreover, the glycemia levels correlated inversely with the level of skeletal glucose uptake, and pharmacological treatment with the glycolysis inhibitor dichloroacetate (DCA), which restored glucose metabolism in Vhl-deficient osteogenic cells in vitro, prevented the development of the systemic metabolic phenotype in the mutant mice. Altogether, these findings reveal a novel link between cellular glucose metabolism in osteoblasts and whole-body glucose homeostasis, controlled by local hypoxia signaling in the skeleton.
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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.