ArticleArthritis and rheumatism2011
Hypoxic regulation of β-1,3-glucuronyltransferase 1 expression in nucleus pulposus cells of the rat intervertebral disc: role of hypoxia-inducible factor proteins.
Article in Arthritis and rheumatism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Role of Advanced Glycation End Products in Intervertebral Disc Degeneration: Mechanism and Therapeutic Potential.Oxidative medicine and cellular longevity · 2022Review
- Regeneration in Spinal Disease: Therapeutic Role of Hypoxia-Inducible Factor-1 Alpha in Regeneration of Degenerative Intervertebral Disc.International journal of molecular sciences · 2021Review
- High-Oxygen Submersion Fetal Thymus Organ Cultures Enable FOXN1-Dependent and -Independent Support of T Lymphopoiesis.Frontiers in immunology · 2021Article
- Effect of diminished flow in rabbit lumbar arteries on intervertebral disc matrix changes using MRI T2-mapping and histology.BMC musculoskeletal disorders · 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
- RNA sequencing identifies gene regulatory networks controlling extracellular matrix synthesis in intervertebral disk tissues.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018Article
- Hypoxia-inducible factor (HIF)-1alpha knockout accelerates intervertebral disc degeneration in mice.International journal of clinical and experimental pathology · 2018Article
- Mucin 1, a signal transduction membrane-bound mucin, is present in human disc tissue and is downregulated in vitro by exposure to IL-1ß or TNF-α.BMC musculoskeletal disorders · 2017Article
- Cell therapy for intervertebral disc repair: Clinical perspective.Journal of orthopaedic translation · 2017Review
- Molecular mechanisms of biological aging in intervertebral discs.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2016Review
- Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells.Oncotarget · 2015Article
- Stem cell therapy for intervertebral disc regeneration: obstacles and solutions.Nature reviews. Rheumatology · 2015Review
- 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
- Understanding nucleus pulposus cell phenotype: a prerequisite for stem cell based therapies to treat intervertebral disc degeneration.Current stem cell research & therapy · 2015Review
- 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
- Smad3 controls β-1,3-glucuronosyltransferase 1 expression in rat nucleus pulposus cells: implications of dysregulated expression in disc disease.Arthritis and rheumatism · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo determine whether hypoxia and hypoxia-inducible factor (HIF) proteins regulate expression of β-1,3-glucuronyltransferase 1 (GlcAT-1), a key enzyme in glycosaminoglycan synthesis in nucleus pulposus cells.
methodsReal-time reverse transcriptase-polymerase chain reaction and Western blotting were used to measure GlcAT-1 expression. Transfections were performed to determine the effect of HIF-1α and HIF-2α on GlcAT-1 promoter activity.
resultsUnder hypoxic conditions there was an increase in GlcAT-1 expression; a significant increase in promoter activity was seen both in nucleus pulposus cells and in N1511 chondrocytes. We investigated whether HIF controlled GlcAT-1 expression. Suppression of HIF-1α and HIF-2α induced GlcAT-1 promoter activity and expression only in nucleus pulposus cells. Transfection with CA-HIF-1α as well as with CA-HIF-2α suppressed GlcAT-1 promoter activity only in nucleus pulposus cells, suggesting a cell type-specific regulation. Site-directed mutagenesis and deletion constructs were used to further confirm the suppressive effect of HIFs on GlcAT-1 promoter function in nucleus pulposus cells. Although it was evident that interaction of HIF with hypoxia-responsive elements resulted in suppression of basal promoter activity, it was not necessary for transcriptional suppression. This result suggested both a direct and an indirect mode of regulation, possibly through recruitment of a HIF-dependent repressor. Finally, we showed that hypoxic expression of GlcAT-1 was also partially dependent on MAPK signaling.
conclusionThese studies demonstrate that hypoxia regulates GlcAT-1 expression through a signaling network comprising both activator and suppressor molecules, and that this regulation is unique to nucleus pulposus cells.
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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.