ArticleMatrix biology : journal of the International Society for Matrix Biology2020
TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 65 citations in OpenAlex.
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- Akkermansia muciniphila attenuates intervertebral disc degeneration via extracellular vesicle-mediated delivery of the effector protein B2UKX5.Bone research · 2026Article
- Causal associations between abdominal obesity, dietary patterns, and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study with clinical validation.Frontiers in medicine · 2026Article
- Age and Spinal Level as Predictors of Lumbar Disc Degeneration in Humans and Mice: A Comparative Analysis.JOR spine · 2025Article
- Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice.Science advances · 2025Article
- Article
- CircFUNDC1 interacts with CDK9 to promote mitophagy in nucleus pulposus cells under oxidative stress and ameliorates intervertebral disc degeneration.Cell death & disease · 2025Article
- Downregulation of aquaporin 3 promotes hyperosmolarity-induced apoptosis of nucleus pulposus cells through PI3K/Akt/mTOR pathway suppression.Frontiers in genetics · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- An anti-FAP-scFv-functionalized exosome-carrying hydrogel deliversTheranostics · 2025Article
- A comparative analysis of TonEBP conditional knockout mouse models reveals inter-dependency between compartments of the intervertebral disc.Development (Cambridge, England) · 2024Article
- Intervertebral disc-intrinsic Hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms.Cellular and molecular life sciences : CMLS · 2024Article
- A new perspective on intervertebral disc calcification-from bench to bedside.Bone research · 2024Review
- Protective effects of Shensuitongzhi formula on intervertebral disc degeneration via downregulation of NF-κB signaling pathway and inflammatory response.Journal of orthopaedic surgery and research · 2024Article
- Increased HIF-2α activity in the nucleus pulposus causes intervertebral disc degeneration in the aging mouse spine.Frontiers in cell and developmental biology · 2024Article
- Molecular mechanism and therapeutic potential of HDAC9 in intervertebral disc degeneration.Cellular & molecular biology letters · 2023Article
- Achilles' Heel-The Significance of Maintaining Microenvironmental Homeostasis in the Nucleus Pulposus for Intervertebral Discs.International journal of molecular sciences · 2023Review
- Intervertebral Disc-on-a-ChipAdvanced materials technologies · 2023Article
- 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
- Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The tonicity-responsive enhancer binding protein (TonEBP) plays an important role in intervertebral disc and axial skeleton embryogenesis. However, the contribution of this osmoregulatory transcription factor in postnatal intervertebral disc homeostasis is not known in vivo. Here, we show for the first time that TonEBP-deficient mice have pronounced age-related degeneration of the intervertebral disc with annular and endplate herniations. Using FTIR-imaging spectroscopy, quantitative immunohistochemistry, and tissue-specific transcriptomic analysis, we provide morphological and molecular evidence that the overall phenotype is driven by a replacement of water-binding proteoglycans with fibrocartilaginous matrix. Whereas TonEBP deficiency in the AF compartment caused tissue fibrosis associated with alterations in actin cytoskeleton and adhesion molecules, predominant changes in pro-inflammatory pathways were seen in the NP compartment of mutants, underscoring disc compartment-specific effects. Additionally, TonEBP-deficient mice presented with compromised trabecular bone properties of vertebrae. These results provide the first in vivo support to the long-held hypothesis that TonEBP is crucial for postnatal homeostasis of the spine and controls a multitude of functions in addition to cellular osmoadaptation.
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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.