ReviewNature reviews. Rheumatology2021
The role of HIF proteins in maintaining the metabolic health of the intervertebral disc.
Review in Nature reviews. Rheumatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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.
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Who cites it
69 citing papers in PubMed, 102 citations in OpenAlex.
- Ubiquitination-mediated degradation of NLRX1 drives metabolic vulnerability and accelerates intervertebral disc degeneration.Cell death and differentiation · 2026Article
- Gut-Intervertebral Disc Axis: Gut Microbiome-Driven Immune-Metabolic Imbalance and Intervertebral Disc Degeneration.Journal of cellular physiology · 2026Review
- Review
- An ECM-mimetic hydrogel for disc repair: reconstituting hypoxia and alleviating NPC senescence to halt intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- HK1-LDHA axis feedback regulation promotes histone lactylation of Wnt5a and mediates prenatal acetaminophen-induced susceptibility to osteoarthritis in male offspring.Experimental & molecular medicine · 2026Article
- Biomaterial-based strategies targeting ferroptosis for alleviating intervertebral disc degeneration: Advances and perspectives.Journal of orthopaedic translation · 2026Review
- Preconditioning Mesenchymal Stem Cells to Enhance Performance in the Degenerate Nucleus Pulposus.Tissue engineering. Part B, Reviews · 2026Review
- Loss of MCT1 mediated lactate uptake causes delayed endplate maturation and intervertebral disc degeneration.Cell death & disease · 2026Article
- Lactate metabolism reprogramming through orthogonal tandem catalysis to reverse intervertebral disc degeneration.Nature communications · 2026Article
- Efficacy and Mechanisms of Duhuo Jisheng Decoction in Treating Intervertebral Disc Degeneration: A Network Pharmacology and Experimental Study.Current medical science · 2026Article
- Natural photosynthetic system for restoring homeostasis of animal organelle interaction network.Nature communications · 2026Article
- Loss of CA12 drive proliferation and fibrosis in type i congenital pulmonary airway malformation via promoting abnormal activation of SHH signaling.Cell communication and signaling : CCS · 2026Article
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Immunometabolism: A Novel Therapeutic Target and Its Pharmacological Modulation for Intervertebral Disc Degeneration.International journal of molecular sciences · 2026Review
- Lactate Metabolism in the Intervertebral Disc: Mechanistic Insights and Pathological Implications.Biomolecules · 2026Review
- Research progress on protein lactylation in female reproductive disease: molecular mechanisms, functions, and therapeutic implications.Frontiers in pharmacology · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- HIF-1α-centered metabolic reprogramming in osteoarthritis: cell type-specific effects and intercellular crosstalk among chondrocytes, BMSCs, and macrophages.Frontiers in immunology · 2026Review
- Stress-response exhaustion in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2026Review
- Hypoxic microenvironment and pulmonary hypertension.Respiratory research · 2025Review
9 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
4 authors at 3 institutions in 1 country.
Funding
Abstract
The physiologically hypoxic intervertebral disc and cartilage rely on the hypoxia-inducible factor (HIF) family of transcription factors to mediate cellular responses to changes in oxygen tension. During homeostatic development, oxygen-dependent prolyl hydroxylases, circadian clock proteins and metabolic intermediates control the activities of HIF1 and HIF2 in these tissues. Mechanistically, HIF1 is the master regulator of glycolytic metabolism and cytosolic lactate levels. In addition, HIF1 regulates mitochondrial metabolism by promoting flux through the tricarboxylic acid cycle, inhibiting downsteam oxidative phosphorylation and controlling mitochondrial health through modulation of the mitophagic pathway. Accumulation of metabolic intermediates from HIF-dependent processes contribute to intracellular pH regulation in the disc and cartilage. Namely, to prevent changes in intracellular pH that could lead to cell death, HIF1 orchestrates a bicarbonate buffering system in the disc, controlled by carbonic anhydrase 9 (CA9) and CA12, sodium bicarbonate cotransporters and an intracellular H
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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.