ArticleAging cell2018
FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 92 citations in OpenAlex.
- The role and potential therapeutic intervention of cellular senescence in intervertebral disc degeneration.Genes & diseases · 2026Review
- TIE2-positive cells in the nucleus pulposus with a purpose: the who, what and why.Journal of biomedical science · 2026Review
- Article
- Immunohistochemical analysis to detect a molecular signature in intervertebral disc degeneration.Histochemistry and cell biology · 2025Article
- Advantages and Possibility of Transcription Factors FOXOs in HCC.Cell biochemistry and function · 2025Review
- Recent Developments in Osteoarthritis Research: Innovative Therapeutic Approaches and the Role of Polyphenols and Nanotechnology.International journal of molecular sciences · 2025Review
- Brachyury-Activated Fucoidan Hydrogel Microspheres Rejuvenate Degenerative Intervertebral Discs Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Sequentially assembled co-delivery nanoplatform of SIRT1 protein and SOX9-expressing plasmid for multipronged therapy of intervertebral disc degeneration.Journal of nanobiotechnology · 2025Article
- 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
- Disc inflammation and intercellular communication in shaping the immune microenvironment of intervertebral disc degeneration.Frontiers in immunology · 2025Article
- pH: A major player in degenerative intervertebral disks.JOR spine · 2024Review
- Procyanidin C1 ameliorates acidic pH stress induced nucleus pulposus degeneration through SIRT3/FOXO3-mediated mitochondrial dynamics.Journal of translational medicine · 2024Article
- Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain.Biomaterials · 2024Article
- Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling.Protein & cell · 2024Article
- Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus.Biomedicines · 2024Article
- Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health.JOR spine · 2024Article
- Dynamics of N6-methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc.JOR spine · 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
- Molecular mechanism and therapeutic potential of HDAC9 in intervertebral disc degeneration.Cellular & molecular biology letters · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Intervertebral disk (IVD) degeneration is a prevalent age-associated musculoskeletal disorder and a major cause of chronic low back pain. Aging is the main risk factor for the disease, but the molecular mechanisms regulating IVD homeostasis during aging are unknown. The aim of this study was to investigate the function of FOXO, a family of transcription factors linked to aging and longevity, in IVD aging and age-related degeneration. Conditional deletion of all FOXO isoforms (FOXO1, 3, and 4) in IVD using the Col2a1Cre and AcanCreER mouse resulted in spontaneous development of IVD degeneration that was driven by severe cell loss in the nucleus pulposus (NP) and cartilaginous endplates (EP). Conditional deletion of individual FOXO in mature mice showed that FOXO1 and FOXO3 are the dominant isoforms and have redundant functions in promoting IVD homeostasis. Gene expression analyses indicated impaired autophagy and reduced antioxidant defenses in the NP of FOXO-deficient IVD. In primary human NP cells, FOXO directly regulated autophagy and adaptation to hypoxia and promoted resistance to oxidative and inflammatory stress. Our findings demonstrate that FOXO are critical regulators of IVD homeostasis during aging and suggest that maintaining or restoring FOXO expression can be a therapeutic strategy to promote healthy IVD aging and delay the onset of IVD degeneration.
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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.