ArticlePhysiological genomics2011
Ascorbic acid regulates osterix expression in osteoblasts by activation of prolyl hydroxylase and ubiquitination-mediated proteosomal degradation pathway.
Article in Physiological genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Pooled it
- Insights into vitamin C in musculoskeletal physiology and disorders: mechanisms and translational perspectives.Frontiers in immunology · 2026Review
- Molecular crosstalk in SP7-mediated osteogenesis: Regulatory mechanisms and therapeutic potential.Osteoporosis and sarcopenia · 2025Review
- Defining the Most Potent Osteoinductive Culture Conditions for MC3T3-E1 Cells Reveals No Implication of Oxidative Stress or Energy Metabolism.International journal of molecular sciences · 2024Article
- Role of vitamins beyond vitamin DInternational journal of molecular medicine · 2024Review
- Deubiquitinase USP17 Regulates Osteoblast Differentiation by Increasing Osterix Protein Stability.International journal of molecular sciences · 2023Article
- Sequential application of small molecule therapy enhances chondrogenesis and angiogenesis in murine segmental defect bone repair.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Lack of Skeletal Effects in Mice with Targeted Disruptionof Prolyl Hydroxylase Domain 1 (Life (Basel, Switzerland) · 2022Article
- Article
- Role of prolyl hydroxylase domain proteins in bone metabolism.Osteoporosis and sarcopenia · 2022Review
- Targeted Deletion of theFrontiers in endocrinology · 2022Article
- Experimental study of the effects of hypoxia simulator on osteointegration of titanium prosthesis in osteoporotic rats.BMC musculoskeletal disorders · 2021Article
- Article
- Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells.Molecular medicine reports · 2020Article
- Hypoxia Signaling in the Skeleton: Implications for Bone Health.Current osteoporosis reports · 2019Review
- Conditional disruption of theBone research · 2019Article
- Vitamin C effects on 5-hydroxymethylcytosine and gene expression in osteoblasts and chondrocytes: Potential involvement of PHD2.PloS one · 2019Article
- LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L-plastin.Journal of cellular biochemistry · 2018Article
- Small molecules modified biomimetic gelatin/hydroxyapatite nanofibers constructing an ideal osteogenic microenvironment with significantly enhanced cranial bone formation.International journal of nanomedicine · 2018Article
- Conditional Deletion of the Phd2 Gene in Articular Chondrocytes Accelerates Differentiation and Reduces Articular Cartilage Thickness.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Mouse genetic studies reveal that ascorbic acid (AA) is essential for osteoblast (OB) differentiation and that osterix (Osx) was a key downstream target of AA action in OBs. To determine the molecular pathways for AA regulation of Osx expression, we evaluated if AA regulates Osx expression by regulating production and/or actions of local growth factors and extracellular matrix (ECM) proteins. Inhibition of actions of IGFs by inhibitory IGFBP-4, BMPs by noggin, and ECM-mediated integrin signaling by RGD did not block AA effects on Osx expression in OBs. Furthermore, blockade of components of MAPK signaling pathway had no effect on AA-induced Osx expression. Because AA is required for prolyl hydroxylase domain (PHD) activity and because PHD-induced prolyl-hydroxylation targets proteins to proteosomal degradation, we next tested if AA effect on Osx expression involves activation of PHD to hydroxylate and induce ubiquitin-proteosome-mediated degradation of transcriptional repressor(s) of Osx gene. Treatment of OBs with dimethyloxallyl glycine and ethyl 3, 4-dihydroxybenzoate, known inhibitors of PHD, completely blocked AA effect on Osx expression and OB differentiation. Knockdown of PHD2 expression by Lentivirus-mediated shRNA abolished AA-induced Osx induction and alkaline phosphatase activity. Furthermore, treatment of OBs with MG115, inhibitor of proteosomal degradation, completely blocked AA effects on Osx expression. Based on these data, we conclude that AA effect on Osx expression is mediated via a novel mechanism that involves PHD2 and proteosomal degradation of a yet to be identified transcriptional repressor that is independent of BMP, IGF-I, or integrin-mediated signaling in mouse OBs.
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What OpenQuestion holds
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.