ArticleArthritis and rheumatism2009
Regulation of autophagy in human and murine cartilage: hypoxia-inducible factor 2 suppresses chondrocyte autophagy.
Article in Arthritis and rheumatism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 133 citations in OpenAlex.
- The Anti-Osteoarthritis Effect of Medicinal and Edible Homologous Bioactive Components and Chinese Medicinal and Health Food Varieties.Nutrients · 2026Review
- Programmed Cell Death of Chondrocytes, Synovial Cells, Osteoclasts, and Subchondral Bone Cells in Osteoarthritis.Journal of inflammation research · 2025Review
- Modulating Autophagy in Osteoarthritis: Exploring Emerging Therapeutic Drug Targets.International journal of molecular sciences · 2024Review
- Cartilage Homeostasis under Physioxia.International journal of molecular sciences · 2024Review
- Synovial Membrane Is a Major Producer of Extracellular Inorganic Pyrophosphate in Response to Hypoxia.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Screening and identification of microRNAs mediating cartilage endplate degeneration in human intervertebral disks.Frontiers in medicine · 2024Article
- The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy.International journal of molecular sciences · 2023Review
- Conditional Deletion of HIF-2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age-Dependent Structural Changes in Intervertebral Disc.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair.International journal of molecular sciences · 2022Review
- Hypoxia-inducible factor expression is related to apoptosis and cartilage degradation in temporomandibular joint osteoarthritis.BMC musculoskeletal disorders · 2022Article
- Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions.International journal of molecular sciences · 2022Review
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner.Cell proliferation · 2021Article
- Human Osteochondral Explants: Reliable Biomimetic Models to Investigate Disease Mechanisms and Develop Personalized Treatments for Osteoarthritis.Rheumatology and therapy · 2021Article
- The function of lncRNAs in the pathogenesis of osteoarthritis.Bone & joint research · 2021Article
- Intra-articular etanercept attenuates pain and hypoxia from TMJ loading in the rat.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Functional Interaction of Hypoxia-Inducible Factor 2-Alpha and Autophagy Mediates Drug Resistance in Colon Cancer Cells.Cancers · 2019Article
- Article
- Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage.Bone & joint research · 2018Article
- Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis.International journal of molecular sciences · 2018Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe have previously demonstrated that the transcription factor hypoxia-inducible factor 1 (HIF-1) promotes the onset of autophagy in chondrocytes. The overall goal of this study was to test the hypothesis that another HIF family transcription factor, HIF-2, modulates the induction of autophagy by chondrocytes.
methodsExpression of HIF-1, HIF-2, and light chain 3 (LC3) in human and murine articular cartilage was visualized by immunohistochemistry. Suppression of HIF-2 was achieved using small interfering RNA technology. Assessments of autophagic flux and lysosomal activity, as well as ultrastructural analysis, were performed in chondrocytes in cell culture.
resultsHIF-2 was expressed abundantly by cells in human and murine articular cartilage and in the cartilage of mineralizing vertebrae from neonatal mice. Protein levels were reduced in articular cartilage from older mice, in end-plate cartilage from mice, and in chondrocytes from human osteoarthritic (OA) cartilage. HIF-2 was robustly expressed in the prehypertrophic cells of mouse growth cartilage. When HIF-2alpha was silenced, the generation of reactive oxygen species was found to be elevated, with a concomitant decrease in catalase and superoxide dismutase activity. Suppression of HIF-2 was associated with decreased Akt-1 and mammalian target of rapamycin activities, reduced Bcl-xL expression, and a robust autophagic response, even under nutrient-replete conditions. In these silenced chondrocytes, HIF-1 expression was elevated. Decreased HIF-2 expression was associated with autophagy in OA tissues and aging cartilage samples. The autophagic response of chondrocytes in HIF-2alpha-knockout mouse growth plate showed an elevated autophagic response throughout the plate.
conclusionBased on these observations, we conclude that HIF-2 is a potent regulator of autophagy in maturing chondrocytes. Our data suggest that this protein acts as a brake on the autophagy-accelerator function of HIF-1.
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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.