ArticleNature medicine2010
Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 319 papers, 1 of them a synthesis that pooled it.
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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
319 citing papers in PubMed, 1 synthesis or guideline pooled it, 513 citations in OpenAlex.
- Evaluating the Effect of Hypoxia on Human Adult Mesenchymal Stromal Cell Chondrogenesis In VitroInternational journal of molecular sciences · 2022Pooled it
- Deciphering the function and mechanism of extracorporeal shock wave therapy in knee osteoarthritis (Review).International journal of molecular medicine · 2026Review
- The Role of Metals and Trace Elements in the Pathogenesis of Osteoarthritis and Other Rheumatic Diseases.International journal of molecular sciences · 2026Review
- Engineered Cyanobacteria-Hydrogel Microecological System for Oxygen Reprogramming Synergizes Immunomodulation With Anabolism in Osteoarthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From Joint Loading to Osteoarthritis: A Multiscale Review of Knee Mechanobiology and Digital Modelling.International journal of molecular sciences · 2026Review
- Review
- Mechanistic Links Underlying the Comorbidity of Osteoporosis and Osteoarthritis: Cell Fate Plasticity Driven by the Subchondral Bone Microenvironment.International journal of molecular sciences · 2026Review
- Review
- IL-1β/EPAS1-Associated Ferroptotic Stress Impairs Skeletal Stem/Progenitor Cell Function in Inflammation-Associated Fracture Nonunion.Current issues in molecular biology · 2026Article
- HIF-2Osteoarthritis and cartilage open · 2026Article
- UBE2M deficiency in alveolar macrophages promotes emphysema through HIF-2α/MMP12 axis.Chinese medical journal pulmonary and critical care medicine · 2026Article
- YTHDF2-driven degradation of BARX2 mRNA accelerates osteoarthritis progression by enhancing the TOP2A/WNT/β-Catenin axis.Communications biology · 2026Article
- Cellular Products with Anti-Inflammatory Properties for the Treatment of Cartilage Lesions.International journal of molecular sciences · 2026Review
- Spatial lipid-barrier coupling in knee osteoarthritis: a mechanism-based perspective centered on the infrapatellar fat pad.Therapeutic advances in musculoskeletal disease · 2026Review
- Hypoxia-Inducible Factors in Rheumatoid Arthritis: Central Pathogenic Roles and Therapeutic Opportunities.Journal of inflammation research · 2026Review
- HIF-2α drives osteoarthritis progression via suppression of the HDAC4-ATF4-CHOP signaling axis.PloS one · 2026Article
- New therapeutic target for osteoarthritis: modulating immune-metabolic aberrations and micromilieu remodeling in underlying bone.Frontiers in pharmacology · 2026Review
- Lipid-Driven Immunometabolism in Mesenchymal Stromal Cells: A New Axis for Musculoskeletal Regeneration.International journal of molecular sciences · 2025Review
- Joint Acidosis and Acid-Sensing Receptors and Ion Channels in Osteoarthritis Pathobiology and Therapy.Cells · 2025Review
- Recent Developments in Osteoarthritis Research: Innovative Therapeutic Approaches and the Role of Polyphenols and Nanotechnology.International journal of molecular sciences · 2025Review
259 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoarthritic cartilage destruction is caused by an imbalance between anabolic and catabolic factors. Here, we show that hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by EPAS1) is a catabolic transcription factor in the osteoarthritic process. HIF-2alpha directly induces the expression in chondrocytes of genes encoding catabolic factors, including matrix metalloproteinases (MMP1, MMP3, MMP9, MMP12 and MMP13), aggrecanase-1 (ADAMTS4), nitric oxide synthase-2 (NOS2) and prostaglandin-endoperoxide synthase-2 (PTGS2). HIF-2alpha expression was markedly increased in human and mouse osteoarthritic cartilage, and its ectopic expression triggered articular cartilage destruction in mice and rabbits. Moreover, mice transgenic for Epas1 only in chondrocytes showed spontaneous cartilage destruction, whereas heterozygous genetic deletion of Epas1 in mice suppressed cartilage destruction caused by destabilization of the medial meniscus (DMM) or collagenase injection, with concomitant modulation of catabolic factors. Our results collectively demonstrate that HIF-2alpha causes cartilage destruction by regulating crucial catabolic genes.
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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.