ArticleCell metabolism2016
HIF-1α Promotes Glutamine-Mediated Redox Homeostasis and Glycogen-Dependent Bioenergetics to Support Postimplantation Bone Cell Survival.
Article in Cell metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- The influence of hypoxia on tissue regeneration in oral and maxillofacial surgery - a systematic review.Clinical oral investigations · 2026Pooled it
- Significance of GSH and HRedox report : communications in free radical research · 2026Review
- Self-Feeding Living Materials Enabled by Cell Responsive Glycogen Nanoparticles as Metabolic Batteries.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Article
- Exploring the potential application of roxadustat in chronic kidney disease-related osteoporosis based on the regulatory role of HIF-1α in bone metabolism.Histology and histopathology · 2026Review
- Interaction of PEGylated gold nanorods with HIF-1α/Ki-67 in inhibiting immunosuppression and arresting cancer proliferation in murine fibrosarcoma.Scientific reports · 2026Article
- Senescent BMSC-Derived Thbs1 Drives Inflammaging and Impairs Bone Regeneration by Suppressing PINK1/Parkin-Mediated Mitophagy in Macrophages.Aging cell · 2026Article
- Early Biological Orchestration in Fracture Healing: Decoding the Crosstalk between Inflammation, Coagulation, and Metabolism.Stem cell reviews and reports · 2026Review
- Glutamine metabolic stress induces SLC25A6-dependent mitofission via MIC60-MIC19 complex disassembly in colorectal cancer.Cell death & disease · 2026Article
- Crosstalk BetweenCancers · 2026Review
- A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt-MAPK-Nrf2-NF-κB Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Optimized delivery of RNA silencing prolyl hydroxylase domain 2 for enhanced angiogenesis and osteogenesis using bioactive glass scaffolds.Scientific reports · 2025Article
- Dnmt1 determines bone length by regulating energy metabolism of growth plate chondrocytes.Nature communications · 2025Article
- Breaking the vicious cycle: Multifunctional nanomaterials targeting Tumor metabolic reprogramming to overcome T cell exhaustion and bone repair failure in bone tumors.Materials today. Bio · 2025Review
- An "inside-out"-guided genetically engineered hydrogel for augmenting aged bone regeneration.Bioactive materials · 2025Article
- Beyond the tumor: Enhancing pancreatic cancer therapy through glutamine metabolism and innovative drug delivery.Journal of cell communication and signaling · 2025Review
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- Research advances in inflammation and oxidative stress in varicocele-induced male infertility: a narrative review.Asian journal of andrology · 2025Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Cell-based therapy is a promising strategy in regenerative medicine, but the poor survival rate of the implanted cells remains a major challenge and limits clinical translation. We preconditioned periosteal cells to the hypoxic and ischemic environment of the bone defect site by deleting prolyl hydroxylase domain-containing protein 2 (PHD2), resulting in hypoxia-inducible factor 1 alpha (HIF-1α) stabilization. This strategy increased postimplantation cell survival and improved bone regeneration. The enhanced cell viability was angiogenesis independent but relied on combined changes in glutamine and glycogen metabolism. HIF-1α stabilization stimulated glutaminase-mediated glutathione synthesis, maintaining redox homeostasis at baseline and during oxidative or nutrient stress. Simultaneously, HIF-1α signaling increased glycogen storage, preventing an energy deficit during nutrient or oxygen deprivation. Pharmacological inhibition of PHD2 recapitulated the adaptations in glutamine and glycogen metabolism and, consequently, the beneficial effects on cell survival. Thus, targeting cellular metabolism is an appealing strategy for bone regeneration and cell-based therapy in general.
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What OpenQuestion holds
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.