ArticleJCI insight2021
Hypoxia induces DOT1L in articular cartilage to protect against osteoarthritis.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 29 citations in OpenAlex.
- DOT1L-mediated H3K79me3 of ITCH promotes AURKA ubiquitination to suppress ECM degradation in osteoarthritis.Molecular genetics and genomics : MGG · 2026Article
- Engineered Cyanobacteria-Hydrogel Microecological System for Oxygen Reprogramming Synergizes Immunomodulation With Anabolism in Osteoarthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Oxygen tension alters cartilage redox balance in response to traumatic impact.Bone & joint research · 2026Article
- Review
- Mechanoepigenetics in musculoskeletal disease.Osteoarthritis and cartilage · 2026Review
- A Comprehensive Reactive-Oxygen-Species-Scavenging Metal-Organic Framework Orchestrates the AMPK-DOT1L-H3K79me3 Cascade to Alleviate Osteoarthritis.Biomaterials research · 2026Article
- Review
- From mechanism to medicine: The progress and potential of epigenetics in osteoarthritis.Osteoarthritis and cartilage open · 2025Review
- Article
- Article
- Landscape of Histone Posttranslational Modifications in Osteoarthritis.Journal of inflammation research · 2025Review
- Dot1l Regulates the Spontaneous Bone Regeneration of Periosteum-Derived Stem Cells by Regulating Chac1 Expression.Stem cells international · 2025Article
- Glucosamine and Silibinin Alter Cartilage Homeostasis through Glycosylation and Cellular Stresses in Human Chondrocyte Cells.International journal of molecular sciences · 2024Article
- The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe.Histology and histopathology · 2024Review
- Review
- Epigenetics as a Therapeutic Target in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Ion modulatory treatments toward functional self-assembled neocartilage.Acta biomaterialia · 2022Article
- Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions.International journal of molecular sciences · 2022Review
- Articular cartilage hypoxia is a potential target for OA therapy.Nature reviews. Rheumatology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoarthritis is the most prevalent joint disease worldwide, and it is a leading source of pain and disability. To date, this disease lacks curative treatment, as underlying molecular mechanisms remain largely unknown. The histone methyltransferase DOT1L protects against osteoarthritis, and DOT1L-mediated H3K79 methylation is reduced in human and mouse osteoarthritic joints. Thus, restoring DOT1L function seems to be critical to preserve joint health. However, DOT1L-regulating molecules and networks remain elusive, in the joint and beyond. Here, we identified transcription factors and networks that regulate DOT1L gene expression using a potentially novel bioinformatics pipeline. Thereby, we unraveled a possibly undiscovered link between the hypoxia pathway and DOT1L. We provide evidence that hypoxia enhanced DOT1L expression and H3K79 methylation via hypoxia-inducible factor-1 α (HIF1A). Importantly, we demonstrate that DOT1L contributed to the protective effects of hypoxia in articular cartilage and osteoarthritis. Intra-articular treatment with a selective hypoxia mimetic in mice after surgical induction of osteoarthritis restored DOT1L function and stalled disease progression. Collectively, our data unravel a molecular mechanism that protects against osteoarthritis with hypoxia inducing DOT1L transcription in cartilage. Local treatment with a selective hypoxia mimetic in the joint restores DOT1L function and could be an attractive therapeutic strategy 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.