ArticleCommunications biology2024
Differential but complementary roles of HIF-1α and HIF-2α in the regulation of bone homeostasis.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Advances in research on the relationship between mitochondrial dysfunction and osteoporosis: a bibliometric study from 2014 to 2024.Frontiers in medicine · 2025Pooled it
- Intelligent responsive alloy scaffold temporally regulates the immune-osteogenic axis for the treatment of infectious bone defects.Bioactive materials · 2026Article
- Review
- Hypoxia Exacerbates Periapical Periodontitis-Associated Pathological Bone Loss via the Hypoxia-Inducible Factor-2α-Calmodulin-Dependent Protein Kinase IV Axis.Cell proliferation · 2026Article
- Mechanistic Links Underlying the Comorbidity of Osteoporosis and Osteoarthritis: Cell Fate Plasticity Driven by the Subchondral Bone Microenvironment.International journal of molecular sciences · 2026Review
- Roxadustat Inhibits Osteoclast Differentiation and Function by Disrupting Cell Cycle Exit.International journal of molecular sciences · 2026Article
- Bone-seeking nanomaterials for rebalancing bone remodeling in osteoporosis.International journal of pharmaceutics: X · 2026Review
- YBX1 promotes angiogenesis after myocardial infarction by stabilizing HIF1α mRNA via miScience · 2026Article
- Vascular smooth muscle cell state trajectories mediate molecular mechanisms of coronary disease risk.Nature communications · 2026Article
- Mechanosensitive ion channels as novel targets in osteoporosis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- Captivating Synergistic, Dose-Dependent Anticancer Effects of Tumor-Regulation Modulators Chloroquine and Ivermectin Completely Abolished by an Opposing Modulator, Deoxycholic Acid, in Hamster Fibrosarcoma: In Vivo, In Vitro, and Literature Review.Pharmaceuticals (Basel, Switzerland) · 2026Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Adaptive hydrogel platforms for infected bone defect repair: microenvironmental responsiveness, osteoimmunomodulation, and regenerative remodeling.Frontiers in bioengineering and biotechnology · 2026Review
- HIF-1α at the intersection of hypoxia, ferroptosis-associated stress, and cell death crosstalk in osteomyelitis.Frontiers in cell and developmental biology · 2026Review
- Macrophage Hypoxia Signaling Pathways and Their Roles in Sepsis.Journal of inflammation research · 2026Review
- Article
- Vascular Patterning affects Intramembranous Ossification through HIF1α-Vegf Signaling.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
- Oxygen Sensing in Osteocytes: From Physiology to Age-related Osteoporosis.Current osteoporosis reports · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Bone is a highly dynamic tissue undergoing continuous formation and resorption. Here, we investigated differential but complementary roles of hypoxia-inducible factor (HIF)-1α and HIF-2α in regulating bone remodeling. Using RNA-seq analysis, we identified that specific genes involved in regulating osteoblast differentiation were similarly but slightly differently governed by HIF-1α and HIF-2α. We found that increased HIF-1α expression inhibited osteoblast differentiation via inhibiting RUNX2 function by upregulation of Twist2, confirmed using Hif1a conditional knockout (KO) mouse. Ectopic expression of HIF-1α via adenovirus transduction resulted in the increased expression and activity of RANKL, while knockdown of Hif1a expression via siRNA or osteoblast-specific depletion of Hif1a in conditional KO mice had no discernible effect on osteoblast-mediated osteoclast activation. The unexpected outcome was elucidated by the upregulation of HIF-2α upon Hif1a overexpression, providing evidence that Hif2a is a transcriptional target of HIF-1α in regulating RANKL expression, verified through an experiment of HIF-2α knockdown after HIF-1α overexpression. The above results were validated in an ovariectomized- and aging-induced osteoporosis model using Hif1a conditional KO mice. Our findings conclude that HIF-1α plays an important role in regulating bone homeostasis by controlling osteoblast differentiation, and in influencing osteoclast formation through the regulation of RANKL secretion via HIF-2α modulation.
Indexed as
Identifiers
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.