ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
HIF-1-PHD2 axis controls expression of syndecan 4 in nucleus pulposus cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Review
- Review
- Fibro-NPC: a pathogenic subtype identified at single-cell resolution with secreted SFRP4 as a biomarker in intervertebral disc degeneration.Journal of translational medicine · 2025Article
- Proteoglycan Dysfunction: A Common Link Between Intervertebral Disc Degeneration and Skeletal Dysplasia.Neurospine · 2024Article
- Review
- Role of Syndecan-4 in the Inhibition of Articular Cartilage Degeneration in Osteoarthritis.Biomedicines · 2023Article
- Activation of Hypoxia-Inducible Factor-1α Signaling Pathway Has the Protective Effect of Intervertebral Disc Degeneration.International journal of molecular sciences · 2021Article
- Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Xentry-Gap19 inhibits Connexin43 hemichannel opening especially during hypoxic injury.Drug delivery and translational research · 2020Article
- Alterations in ECM signature underscore multiple sub-phenotypes of intervertebral disc degeneration.Matrix biology plus · 2020Article
- Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment.Frontiers in immunology · 2020Article
- Syndecan-4 is a Novel Therapeutic Target for Intervertebral Disc Degeneration via Suppressing JNK/p53 Pathway.International journal of biological sciences · 2020Article
- Exosomes Derived from Human Urine-Derived Stem Cells Inhibit Intervertebral Disc Degeneration by Ameliorating Endoplasmic Reticulum Stress.Oxidative medicine and cellular longevity · 2020Article
- Mechanosensitive transcriptional coactivators MRTF-A and YAP/TAZ regulate nucleus pulposus cell phenotype through cell shape.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Syndecan-4 regulates extravillous trophoblast migration by coordinating protein kinase C activation.Scientific reports · 2019Article
- Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis.Matrix biology : journal of the International Society for Matrix Biology · 2018Article
- Hypoxia-inducible factor (HIF)-1alpha knockout accelerates intervertebral disc degeneration in mice.International journal of clinical and experimental pathology · 2018Article
- Induction of Syndecan-4 by Organic-Inorganic Hybrid Molecules with a 1,10-Phenanthroline Structure in Cultured Vascular Endothelial Cells.International journal of molecular sciences · 2017Article
- Genomic insights into ayurvedic and western approaches to personalized medicine.Journal of genetics · 2016Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Intervertebral disc degeneration is the leading cause of chronic back pain. Recent studies show that raised level of SDC4, a cell-surface heparan sulfate (HS) proteoglycan, plays a role in pathogenesis of disc degeneration. However, in nucleus pulposus (NP) cells of the healthy intervertebral disc, the mechanisms that control expression of SDC4 and its physiological function are unknown. Hypoxia induced SDC4 mRNA and protein expression by ~2.4- and 4.4-fold (P<0.05), respectively, in NP cells. While the activity of the SDC4 promoter containing hypoxia response element (HRE) was induced 2-fold (P<0.05), the HRE mutation decreased the activity by 40% in hypoxia. Transfections with plasmids coding prolyl-4-hydroxylase domain protein 2 (PHD2) and ShPHD2 show that hypoxic expression of SDC4 mRNA and protein is regulated by PHD2 through controlling hypoxia-inducible factor 1α (HIF-1α) levels. Although overexpression of HIF-1α significantly increased SDC4 protein levels, stable suppression of HIF-1α and HIF-1β decreased SDC4 expression by 50% in human NP cells. Finally, suppression of SDC4 expression, as well as HS function, resulted in an ~2-fold increase in sex-determining region Y (SRY)-box 9 (Sox9) mRNA, and protein (P<0.05) and simultaneous increase in Sox9 transcriptional activity and target gene expression. Taken together, our findings suggest that in healthy discs, SDC4, through its HS side chains, contributes to maintenance of the hypoxic tissue niche by controlling baseline expression of Sox9.
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Registered trials
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