ReviewMatrix biology : journal of the International Society for Matrix Biology2014
Extracellular osmolarity regulates matrix homeostasis in the intervertebral disc and articular cartilage: evolving role of TonEBP.
Review in Matrix biology : journal of the International Society for Matrix Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 122 citations in OpenAlex.
- Persistent ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives.Theranostics · 2026Review
- Understanding the Physiological Behavior of Disc Cells in an In Vitro Imitation of the Healthy and Degenerated Disc Niche.JOR spine · 2025Article
- Review
- A Multidimensional Definition of Pre-Osteoarthritis: Toward 21st-Century Subclinical Detection and Targeted Intervention.International journal of molecular sciences · 2025Review
- SOX4 accelerates intervertebral disc degeneration via EZH2/NRF2 pathway in response to mitochondrial ROS-dependent NLRP3 inflammasome activation in nucleus pulposus cells.Journal of translational medicine · 2025Article
- Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties.International journal of molecular sciences · 2025Review
- Stem cell-based strategies for intervertebral disc regeneration in degenerative microenvironments: challenges and solutions.Frontiers in cell and developmental biology · 2025Review
- Role of Galectin-3 in intervertebral disc degeneration: an experimental study.BMC musculoskeletal disorders · 2024Article
- Osmolarity-Induced Altered Intracellular Molecular Crowding Drives Osteoarthritis Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Therapeutic targets and potential delivery systems of melatonin in osteoarthritis.Frontiers in immunology · 2024Review
- Achilles' Heel-The Significance of Maintaining Microenvironmental Homeostasis in the Nucleus Pulposus for Intervertebral Discs.International journal of molecular sciences · 2023Review
- Review
- Conditional Deletion of HIF-2α in Mouse Nucleus Pulposus Reduces Fibrosis and Provides Mild and Transient Protection From Age-Dependent Structural Changes in Intervertebral Disc.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Changes in Elements and Relationships among Elements in Intervertebral Disc Degeneration.International journal of environmental research and public health · 2022Article
- Physosmotic Induction of Chondrogenic Maturation Is TGF-β Dependent and Enhanced by Calcineurin Inhibitor FK506.International journal of molecular sciences · 2022Article
- Article
- CB2R Attenuates Intervertebral Disc Degeneration by Delaying Nucleus Pulposus Cell Senescence through AMPK/GSK3β Pathway.Aging and disease · 2022Article
- Long intergenic non-coding RNA -00917 regulates the proliferation, inflammation, and pyroptosis of nucleus pulposus cells via targeting miR-149-5p/NOD-like receptor protein 1 axis.Bioengineered · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Degeneration of the intervertebral disc is characterized by changes in proteoglycan status, loss of bound water molecules, decreased tissue osmotic pressure and a resulting mechanical failure of the disc. A similar spectrum of changes is evident in osteoarthritic articular cartilage. When healthy, resident cells in these skeletal tissues respond to applied mechanical loads by regulating their own osmotic state and the hydration of the extracellular matrix. The transcription factor Tonicity-Responsive Enhancer Binding Protein (TonEBP or NFAT5) is known to mediate the osmoadaptive response in these and other tissues. While the molecular basis of how osmotic loading controls matrix homeostasis is not completely understood, TonEBP regulates the expression of aggrecan and β1,3-glucoronosyltransferase in nucleus pulposus cells, in addition to targets that allow for survival under hypertonic stress. Moreover, in chondrocytes, TonEBP controls expression of several collagen subtypes and Sox9, a master regulator of aggrecan and collagen II expression. Thus, TonEBP-mediated regulation of the matrix composition allows disc cells and chondrocytes to modify the extracellular osmotic state itself. On the other hand, TonEBP in immune cells induces expression of TNF-α, ΙL-6 and MCP-1, pro-inflammatory molecules closely linked to matrix catabolism and pathogenesis of both disc degeneration and osteoarthritis, warranting investigations of this aspect of TonEBP function in skeletal cells. In summary, the TonEBP system, through its effects on extracellular matrix and osmoregulatory genes can be viewed primarily as a protective or homeostatic response to physiological loading.
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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.