ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2009
Osmolarity and intracellular calcium regulate aquaporin2 expression through TonEBP in nucleus pulposus cells of the intervertebral disc.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- A comparative analysis of TonEBP conditional knockout mouse models reveals inter-dependency between compartments of the intervertebral disc.Development (Cambridge, England) · 2024Article
- Proteoglycan Dysfunction: A Common Link Between Intervertebral Disc Degeneration and Skeletal Dysplasia.Neurospine · 2024Article
- Article
- Edifying the Focal Factors Influencing Mesenchymal Stem Cells by the Microenvironment of Intervertebral Disc Degeneration in Low Back Pain.Pain research & management · 2022Review
- Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs.Bone research · 2021Article
- The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases.Scientific reports · 2021Article
- TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc.Scientific reports · 2021Article
- Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.International journal of molecular sciences · 2021Review
- TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Nucleus pulposus primary cilia alter their length in response to changes in extracellular osmolarity but do not control TonEBP-mediated osmoregulation.Scientific reports · 2019Article
- Hyper-osmolarity environment-induced oxidative stress injury promotes nucleus pulposus cell senescenceBioscience reports · 2019Article
- Sickle cell disease up-regulates vasopressin, aquaporin 2, urea transporter A1, Na-K-Cl cotransporter 2, and epithelial Na channels in the mouse kidney medulla despite compromising urinary concentration ability.Physiological reports · 2019Article
- Aquaporin expression in the human and canine intervertebral disc during maturation and degeneration.JOR spine · 2019Article
- Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering.Stem cells international · 2019Review
- COX-2 expression mediated by calcium-TonEBP signaling axis under hyperosmotic conditions serves osmoprotective function in nucleus pulposus cells.The Journal of biological chemistry · 2018Article
- Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation.Oncotarget · 2017Review
- Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus.Scientific reports · 2017Article
- RNA Sequencing Reveals a Role of TonEBP Transcription Factor in Regulation of Pro-inflammatory Genes in Response to Hyperosmolarity in Healthy Nucleus Pulposus Cells: A HOMEOSTATIC RESPONSE?The Journal of biological chemistry · 2016Article
- Osmolar regulation of endothelin-1 production by the inner medullary collecting duct.Life sciences · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The goal of this study was to examine the expression and regulation of aquaporin2 (AQP2), a tonicity-sensitive water channel in nucleus pulposus cells of the intervertebral disc. We found that AQP2 protein was expressed in vivo in both rat and human discs. We determined whether AQP2 promoter expression was regulated by osmolarity in a tonicity enhancer binding protein (TonEBP)-dependent manner.When TonEBP was suppressed under hypertonic conditions or overexpressed under isotonic conditions,AQP2 promoter activity was correspondingly inhibited or induced. The role of TonEBP in controlling AQP2 expression was confirmed using mouse embryonic fibroblasts (MEFs) derived from TonEBP-null mice. We studied whether calcium in addition to osmolarity played a role in regulation of AQP2 in nucleus pulposus cells. We also determined whether both TonEBP and calcineurin-nuclear factor of activated T cells (NFAT)signaling contributed to ionomycin, a calcium ionophore, mediated induction of AQP2. Co-transfection of AQP2 reporter with calcineurin (CnA/B) and/or NFAT1-4 vectors suggested that this pathway did not control AQP2 promoter activity in nucleus pulposus cells. These findings were also validated using MEFs from TonEBP, fibroblasts from CnAalpha- and CnAbeta-null mice, and mutant TonE reporter constructs. Results of these studies suggest that, in nucleus pulposus cells, osmotic pressure and calcium modulate AQP2 expression through TonEBP and are independent of the calcineurin-NFAT pathway. Because calcium flux reflects a change in applied stress, the possibility exists that NFAT5/TonEBP modulate not just water balance in the disc but also accommodate applied biomechanical forces.
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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.