ArticleArthritis and rheumatism2010
Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: possible implications in controlling dystrophic mineralization in the intervertebral disc.
Article in Arthritis and rheumatism, 2010. 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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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Resetting the epigenetic clock: cellular senescence and regenerative strategies in intervertebral disc degeneration.Frontiers in aging · 2026Review
- Loss of function mutation in Ank causes aberrant mineralization and acquisition of osteoblast-like-phenotype by the cells of the intervertebral disc.Cell death & disease · 2023Article
- Nutrient metabolism of the nucleus pulposus: A literature review.North American Spine Society journal · 2023Article
- Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment.Frontiers in immunology · 2023Review
- Article
- Regeneration in Spinal Disease: Therapeutic Role of Hypoxia-Inducible Factor-1 Alpha in Regeneration of Degenerative Intervertebral Disc.International journal of molecular sciences · 2021Review
- The potential role and trend of HIF‑1α in intervertebral disc degeneration: Friend or foe? (Review).Molecular medicine reports · 2021Review
- High-Oxygen Submersion Fetal Thymus Organ Cultures Enable FOXN1-Dependent and -Independent Support of T Lymphopoiesis.Frontiers in immunology · 2021Article
- Ankylosis progressive homolog upregulation inhibits cell viability and mineralization during fibroblast ossification by regulating the Wnt/β‑catenin signaling pathway.Molecular medicine reports · 2020Article
- Nanofibrous spongy microspheres to deliver rabbit mesenchymal stem cells and anti-miR-199a to regenerate nucleus pulposus and prevent calcification.Biomaterials · 2020Article
- 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
- Demographic History and Genetic Adaptation in the Himalayan Region Inferred from Genome-Wide SNP Genotypes of 49 Populations.Molecular biology and evolution · 2018Article
- Defining the phenotype of young healthy nucleus pulposus cells: recommendations of the Spine Research Interest Group at the 2014 annual ORS meeting.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2015Article
- FIH-1-Mint3 axis does not control HIF-1 transcriptional activity in nucleus pulposus cells.The Journal of biological chemistry · 2014Article
- Regulatory role of hypoxia inducible factor in the biological behavior of nucleus pulposus cells.Yonsei medical journal · 2013Review
- Hypoxia-inducible factor (HIF)-1α and CCN2 form a regulatory circuit in hypoxic nucleus pulposus cells: CCN2 suppresses HIF-1α level and transcriptional activity.The Journal of biological chemistry · 2013Article
- Reconstruction of an in vitro niche for the transition from intervertebral disc development to nucleus pulposus regeneration.Stem cells and development · 2013Review
- Tonicity enhancer binding protein (TonEBP) and hypoxia-inducible factor (HIF) coordinate heat shock protein 70 (Hsp70) expression in hypoxic nucleus pulposus cells: role of Hsp70 in HIF-1α degradation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2012Article
- Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype.Biomaterials · 2011Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveSince nucleus pulposus cells reside under conditions of hypoxia, we determined if the expression of ANK, a pyrophosphate transporter, is regulated by the hypoxia-inducible factor (HIF) proteins.
methodsQuantitative reverse transcription-polymerase chain reaction and Western blot analyses were used to measure ANK expression in nucleus pulposus cells from rats and humans. Transfections were performed to determine the effect of HIF-1/2 on ANK promoter activity.
resultsANK was expressed in embryonic and mature rat discs. Oxygen-dependent changes in ANK expression in nucleus pulposus cells were minimal. However, silencing of HIF-1α and HIF-2α resulted in increased ANK expression and up-regulation of promoter activity. HIF-mediated suppression of ANK was validated by measuring promoter activity in HIF-1β-null embryonic fibroblasts. Under conditions of hypoxia, there was induction of promoter activity in the null cells as compared with the wild-type cells. Overexpression of HIF-1α and HIF-2α in nucleus pulposus cells resulted in a significant suppression of ANK promoter activity. Since the ANK promoter contains 2 hypoxia-responsive elements (HREs), we performed site-directed mutagenesis and measured promoter activity. We found that HIF-1 can bind to either of the HREs and can suppress promoter activity; in contrast, HIF-2 was required to bind to both HREs in order to suppress activity. Finally, analysis of human nucleus pulposus tissue showed that while ANK was expressed in normal tissue, there was increased expression of ANK along with alkaline phosphatase in the degenerated state.
conclusionBoth HIF-1 and HIF-2 serve as negative regulators of ANK expression in the disc. We propose that baseline expression of ANK in the disc serves to prevent mineral formation under physiologic conditions.
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Registered trials
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