ArticleNature medicine2010
Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development.
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 300 papers, 3 of them syntheses that pooled it.
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.
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
300 citing papers in PubMed, 3 syntheses or guidelines pooled it, 502 citations in OpenAlex.
- Bibliometric analysis of research trends and emerging insights of osteoarthritis and chondrocyte hypertrophy.Frontiers in surgery · 2025Pooled it
- MicroRNA expression in osteoarthritis: a meta-analysis.Clinical and experimental medicine · 2023Pooled it
- Pooled it
- Deciphering the function and mechanism of extracorporeal shock wave therapy in knee osteoarthritis (Review).International journal of molecular medicine · 2026Review
- Oxygen Consumption Rate-Defined Phases Couple Metabolism to Matrix Dynamics in Chondrocyte-Mesenchymal Stromal Cell Co-Culture.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- From Joint Loading to Osteoarthritis: A Multiscale Review of Knee Mechanobiology and Digital Modelling.International journal of molecular sciences · 2026Review
- Review
- Transcriptome analysis in osteoarthritis primary tissues identifies high-confidence effector genes.Nature communications · 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
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Critical Overview of Molecular Insights into Osteoarthritis and Therapeutic Targets: Cytokines, RANKL, MMPs, Adipokines and Phosphate Dysregulation.International journal of molecular sciences · 2026Review
- 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
- Mechanobiology of hypertrophic chondrocyte mineralization: Biomechanical regulation and therapeutic implications in skeletal disorders.Mechanobiology in medicine · 2026Review
- Ubiquitin-specific protease 26 facilitates endochondral ossification by driving chondrocyte hypertrophy and mineralization.Bone research · 2026Article
- Review
- α-Ketoglutarate protects against cartilage damage via epigenetically driven metabolic reprogramming in osteoarthritis models.The Journal of clinical investigation · 2026Article
- COL10A1 beyond skeletal development: a hypertrophic chondrocyte-specific collagen emerging as a potential biomarker and tumor microenvironment regulator in solid cancers.American journal of cancer research · 2026Review
- Exploring the intricate relationship between IL-1β and IL-18 in the context of osteoarthritis.Frontiers in immunology · 2026Review
240 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chondrocyte hypertrophy followed by cartilage matrix degradation and vascular invasion, characterized by expression of type X collagen (COL10A1), matrix metalloproteinase-13 (MMP-13) and vascular endothelial growth factor (VEGF), respectively, are central steps of endochondral ossification during normal skeletal growth and osteoarthritis development. A COL10A1 promoter assay identified hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by EPAS1) as the most potent transactivator of COL10A1. HIF-2alpha enhanced promoter activities of COL10A1, MMP13 and VEGFA through specific binding to the respective hypoxia-responsive elements. HIF-2alpha, independently of oxygen-dependent hydroxylation, was essential for endochondral ossification of cultured chondrocytes and embryonic skeletal growth in mice. HIF-2alpha expression was higher in osteoarthritic cartilages versus nondiseased cartilages of mice and humans. Epas1-heterozygous deficient mice showed resistance to osteoarthritis development, and a functional single nucleotide polymorphism (SNP) in the human EPAS1 gene was associated with knee osteoarthritis in a Japanese population. The EPAS1 promoter assay identified RELA, a nuclear factor-kappaB (NF-kappaB) family member, as a potent inducer of HIF-2alpha expression. Hence, HIF-2alpha is a central transactivator that targets several crucial genes for endochondral ossification and may represent a therapeutic target for osteoarthritis.
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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.