ArticleFrontiers in cell and developmental biology2021
Cholesterol Induces Pyroptosis and Matrix Degradation
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
- TDP43 cytoplasmic mislocalization initiates mitochondrial dysfunction and intercellular senescence propagation in intervertebral disc degeneration.Experimental & molecular medicine · 2026Article
- Revisiting intervertebral disc degeneration: lipid metabolism disorders as overlooked contributors to complex pathology.Frontiers in immunology · 2026Review
- Metabolic reprogramming in intervertebral disc degeneration: mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Excessive cholesterol accelerates intervertebral disc degeneration by promoting the polarization of M1 macrophages.Lipids in health and disease · 2025Article
- A Cross-Tissue Transcriptome-Wide Association Study Identified Susceptibility Genes for Intervertebral Disc Degeneration.JOR spine · 2025Article
- SESN2 maintains cartilage homeostasis by SREBP1-mediated lipid metabolism during osteoarthritis progression.iScience · 2025Article
- Activation of LAMP1-mediated lipophagy by sulforaphane inhibits cellular senescence and intervertebral disc degeneration.Journal of orthopaedic translation · 2025Article
- Association between metabolic syndrome and low back pain: a two-sample Mendelian randomization study.Scientific reports · 2025Article
- Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.Journal of advanced research · 2025Review
- Life-threatening risk factors contribute to the development of diseases with the highest mortality through the induction of regulated necrotic cell death.Cell death & disease · 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
- Dissecting Causal Relationships Between Gut Microbiota, 1400 Blood Metabolites, and Intervertebral Disc Degeneration.Neurospine · 2025Article
- The protective effect and experimental research progress of pleotropic statins in intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2025Review
- Quercetin Alleviates Hyperglycemic-Generated Endoplasmic Reticulum Stress-Contacted Apoptosis of Rat Nucleus Pulposus Cells.Balkan medical journal · 2025Article
- Focus on Cell Apoptosis, Pyroptosis and Ferroptosis to Explore Strategic Breakthrough for GDM.Journal of inflammation research · 2025Review
- Lipid metabolic disorders and their impact on cartilage endplate and nucleus pulposus function in intervertebral disk degeneration.Frontiers in nutrition · 2025Review
- ER-resident proteins are key players in cartilage and bone homeostasis.Frontiers in cell and developmental biology · 2025Review
- The muscle-intervertebral disc interaction mediated by L-BAIBA modulates extracellular matrix homeostasis and PANoptosis in nucleus pulposus cells.Experimental & molecular medicine · 2024Article
- Association between lipid-lowering agents with intervertebral disc degeneration, sciatica and low back pain: a drug-targeted mendelian randomized study and cross-sectional observation.Lipids in health and disease · 2024Observational
- An optimized instrument variable selection approach to improve causality estimation in association studies.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intervertebral disc degeneration (IDD) is closely associated with low back pain, but its underlying mechanism remains unclear. Cholesterol is an essential nutrient in mammalian cells. Alterations in cholesterol levels lead to impairments in cell physiology, such as cell proliferation and signal transduction. Previous clinical studies demonstrated that hypercholesterolemia could be a potential risk factor for IDD, but how cholesterol induces IDD remains unknown. The current study aimed to explore the regulatory role of cholesterol in IDD development and the potential underlying mechanisms. It was found that different forms of cholesterol levels were elevated in degenerative nucleus pulposus (NP) tissues in both humans and Sprague-Dawley rats. Rats fed a high cholesterol diet (HCD) exhibited degenerative features in the lumbar intervertebral disc compared with those fed a standard diet. Interestingly, this effect could be abolished by cholesterol-lowering drug atorvastatin. In NP cells treated with TNF-α and IL-1β, a significantly higher level of cholesterol was observed. These results suggested a pivotal role of cholesterol in the progression of IDD. We also observed accelerated pyroptosis in NP cells and extracellular matrix (ECM) degradation in the rat NP cells treated with exogenous cholesterol. We further demonstrated that endoplasmic reticulum stress was responsible for cholesterol-induced pyroptosis and ECM degradation. Moreover, RNA-seq analysis revealed that the mature form of SREBP1 (mSREBP1), an important regulator of lipid metabolism, is involved in regulating endoplasmic reticulum stress in knockdown experiments. In conclusion, this study demonstrated that cholesterol could induce pyroptosis in NP cells and ECM degradation by activating endoplasmic reticulum stress through stimulating mSREBP1 in IDD.
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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.