ArticlePloS one2019
Vitamin C effects on 5-hydroxymethylcytosine and gene expression in osteoblasts and chondrocytes: Potential involvement of PHD2.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis 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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Pooled it
- Elevated DNA 5-hydroxymethylation promotes chondrocyte differentiation via TET-mediated epigenetic downregulation of hTERT in human mesenchymal stem cells.Histochemistry and cell biology · 2026Article
- Bifidobacterium longum CBi0703 lysate modulates oxidative stress induced apoptosis and cartilage related gene expression in SW1353 chondrocytes: in vitro insights into the gut joint axis in Osteoarthritis.Scientific reports · 2026Article
- Insights into vitamin C in musculoskeletal physiology and disorders: mechanisms and translational perspectives.Frontiers in immunology · 2026Review
- Hip Involvement in Pediatric Scurvy: Early Magnetic Imaging Signs.Children (Basel, Switzerland) · 2025Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Enhanced articular cartilage regeneration using costal chondrocyte-derived scaffold-free tissue engineered constructs with ascorbic acid treatment.Journal of orthopaedic translation · 2024Article
- Age-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity.Nature communications · 2023Article
- Vitamin C epigenetically controls osteogenesis and bone mineralization.Nature communications · 2022Article
- Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment.Cancers · 2022Review
- Role of prolyl hydroxylase domain proteins in bone metabolism.Osteoporosis and sarcopenia · 2022Review
- Targeted Deletion of theFrontiers in endocrinology · 2022Article
- Three Classes of Antioxidant Defense Systems and the Development of Postmenopausal Osteoporosis.Frontiers in physiology · 2022Review
- Article
- Ascorbic Acid and Iron Supplement Treatment Improves Stem Cell-Mediated Cartilage Regeneration in a Minipig Model.The American journal of sports medicine · 2021Article
- Vitamin C supplementation for the treatment of osteoarthritis: perspectives on the past, present, and future.Therapeutic advances in chronic disease · 2021Review
- Ascorbic acid promotes the reproductive function of porcine immature Sertoli cells through transcriptome reprogramming.Theriogenology · 2020Article
- Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells.Molecular medicine reports · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Vitamin C (ascorbic acid, AA) is a well-known regulator of bone and cartilage metabolism. However, the mechanisms of AA's action in these tissues are only partly understood. In this study, we confirmed that AA contributes to bone and cartilage metabolism by showing decreased articular cartilage and trabecular bone in AA-deficient spontaneous fracture (sfx) mutant mice. In vitro, we found that AA exerts differential effects on chondrocyte and osteoblast differentiation. Since AA is known to increase levels of 5-hydroxymethylcytosine (5-hmC) and induce DNA demethylation via the ten-eleven translocases (TETs), and since prolyl hydroxylase domain-containing protein 2 (PHD2), a known mediator of AA's effects in these tissues, is part of the same enzyme family as the TETs, we next investigated whether increases in 5-hmC might mediate some of these effects. All TETs and PHDs are expressed in chondrocytes and osteoblasts, and PHD2 is localized in both the cytoplasm and nucleus of the cell, lending plausibility to the hypothesis of altered 5-hmC content in these cells. We found that AA treatment increased levels of 5-hmC in both cell types globally, notably including promoter regions of osteoblast differentiation genes. Furthermore, inhibition of PHD2 decreased 5-hmC levels in chondrocyte differentiation gene promoters, and knockdown of Phd2 in chondrocytes reduced global 5-hmC levels, suggesting for the first time that PHD2 may itself directly mediate increases in 5-hmC in chondrocyte and osteoblast genes. Further investigation of this mechanism could lead to novel therapeutic approaches to treat debilitating diseases such as osteoarthritis and osteoporosis.
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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.