ArticleThe Journal of biological chemistry2018
COX-2 expression mediated by calcium-TonEBP signaling axis under hyperosmotic conditions serves osmoprotective function in nucleus pulposus cells.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Effects of Antibiotics and Anti-Inflammatory Drugs on Enamel Development: A Systematic Review with Quantitative Synthesis.International dental journal · 2026Pooled it
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- During high salt treatment myeloid p38α/MAPK fosters osteoclast activity and inflammatory macrophage responses promoting orthodontic tooth movement.Frontiers in immunology · 2025Article
- Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF-κВ and WNT Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Effect of felodipine on indomethacin-induced gastric ulcers in rats.Experimental animals · 2023Article
- Review
- Article
- TonEBP expression is essential in the IL-1β-induced migration and invasion of human A549 lung cancer cells.Oncology research · 2023Article
- Immuno-Modulatory Effects of Intervertebral Disc Cells.Frontiers in cell and developmental biology · 2022Review
- Zinc(II) niflumato complex effects on MMP activity and gene expression in human endometrial cell lines.Scientific reports · 2021Article
- Article
- The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases.Scientific reports · 2021Article
- Hyperosmolarity benefits cartilage regeneration by enhancing expression of chondrogenic markers and reducing inflammatory markers.In vitro cellular & developmental biology. Animal · 2021Article
- TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc.Scientific reports · 2021Article
- NSP2 Is Important for Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus to Trigger High Fever-Related COX-2-PGE2 Pathway in Pigs.Frontiers in immunology · 2021Article
- Alterations in ECM signature underscore multiple sub-phenotypes of intervertebral disc degeneration.Matrix biology plus · 2020Article
- 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
- Differential Effect of Long-Term Systemic Exposure of TNFα on Health of the Annulus Fibrosus and Nucleus Pulposus of the Intervertebral Disc.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Arp2/3 inactivation causes intervertebral disc and cartilage degeneration with dysregulated TonEBP-mediated osmoadaptation.JCI insight · 2020Article
- Integrated Pathways of COX-2 and mTOR: Roles in Cell Sensing and Alzheimer's Disease.Frontiers in neuroscience · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The nucleus pulposus (NP) of intervertebral discs experiences dynamic changes in tissue osmolarity because of diurnal loading of the spine. TonEBP/NFAT5 is a transcription factor that is critical in osmoregulation as well as survival of NP cells in the hyperosmotic milieu. The goal of this study was to investigate whether cyclooxygenase-2 (COX-2) expression is osmoresponsive and dependent on TonEBP, and whether it serves an osmoprotective role. NP cells up-regulated COX-2 expression in hyperosmotic media. The induction of COX-2 depended on elevation of intracellular calcium levels and p38 MAPK pathway, but independent of calcineurin signaling as well as MEK/ERK and JNK pathways. Under hyperosmotic conditions, both COX-2 mRNA stability and its proximal promoter activity were increased. The proximal COX-2 promoter (-1840/+123 bp) contained predicted binding sites for TonEBP, AP-1, NF-κB, and C/EBP-β. While COX-2 promoter activity was positively regulated by both AP-1 and NF-κB, AP-1 had no effect and NF-κB negatively regulated COX-2 protein levels under hyperosmotic conditions. On the other hand, TonEBP was necessary for both COX-2 promoter activity and protein up-regulation in response to hyperosmotic stimuli.
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Registered trials
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