ArticleOsteoarthritis and cartilage2012
Spine degeneration in a murine model of chronic human tobacco smokers.
Article in Osteoarthritis and cartilage, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Causal links between multi-domain risk factors and intervertebral disc degeneration: a systematic review and meta-analysis of Mendelian randomization studies.BMC musculoskeletal disorders · 2026Pooled it
- PHLPP1 Regulates Inflammatory Signaling in Degenerated Nucleus Pulposus Cells in Mice and Humans.Cells · 2026Article
- Cigarette Smoking Was Not Associated With Lower Odds of Radiographic Fusion After Combined TLIF and Posterolateral Lumbar (270°) Arthrodesis: A CT-based Retrospective Cohort Evaluation.Clinical orthopaedics and related research · 2026Article
- A Comparison of Cigarette Smoking Effects on Intervertebral Disc Cell Metabolism in a Rat Tissue Model.Annals of biomedical engineering · 2026Article
- Akkermansia muciniphila attenuates intervertebral disc degeneration via extracellular vesicle-mediated delivery of the effector protein B2UKX5.Bone research · 2026Article
- Establishment and research progress of animal models for intervertebral disc degeneration.Open life sciences · 2026Article
- Effect of Long-Term Smoking on Cervical Disc Degeneration: A Retrospective Study.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Inflammatory Biomarkers in Smokers: Implications for Ligamentum Flavum Hypertrophy.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Effect of cigarette smoke exposure and cessation on regional diffusion properties in rat intervertebral discs.JOR spine · 2024Article
- Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation.JOR spine · 2024Article
- Causal association of leisure sedentary behavior and cervical spondylosis, sciatica, intervertebral disk disorders, and low back pain: a Mendelian randomization study.Frontiers in public health · 2024Article
- Achilles' Heel-The Significance of Maintaining Microenvironmental Homeostasis in the Nucleus Pulposus for Intervertebral Discs.International journal of molecular sciences · 2023Review
- Patient Optimization for the Prevention of Proximal Junctional Kyphosis.International journal of spine surgery · 2023Article
- Non-spinal low back pain: Global epidemiology, trends, and risk factors.Health science reports · 2023Article
- N6-methyladenosine hypomethylation of circGPATCH2L regulates DNA damage and apoptosis through TRIM28 in intervertebral disc degeneration.Cell death and differentiation · 2023Article
- Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy.North American Spine Society journal · 2023Article
- Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration.Frontiers in pharmacology · 2023Review
- Microgravity and the intervertebral disc: The impact of space conditions on the biomechanics of the spine.Frontiers in physiology · 2023Review
- Percutaneous lumbar annular puncture: A rat model to study intervertebral disc degeneration and pain-related behavior.JOR spine · 2022Article
- Ionizing Radiation Induces Disc Annulus Fibrosus Senescence and Matrix Catabolism via MMP-Mediated Pathways.International journal of molecular sciences · 2022Article
7 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
12 authors at 4 institutions in 4 countries.
Funding
Abstract
objectiveTo investigate the mechanisms by which chronic tobacco smoking promotes intervertebral disc degeneration (IDD) and vertebral degeneration in mice.
methodsThree month old C57BL/6 mice were exposed to tobacco smoke by direct inhalation (4 cigarettes/day, 5 days/week for 6 months) to model long-term smoking in humans. Total disc proteoglycan (PG) content [1,9-dimethylmethylene blue (DMMB) assay], aggrecan proteolysis (immunobloting analysis), and cellular senescence (p16INK4a immunohistochemistry) were analyzed. PG and collagen syntheses ((35)S-sulfate and (3)H-proline incorporation, respectively) were measured using disc organotypic culture. Vertebral osteoporosity was measured by micro-computed tomography.
resultsDisc PG content of smoke-exposed mice was 63% of unexposed control, while new PG and collagen syntheses were 59% and 41% of those of untreated mice, respectively. Exposure to tobacco smoke dramatically increased metalloproteinase-mediated proteolysis of disc aggrecan within its interglobular domain (IGD). Cellular senescence was elevated two-fold in discs of smoke-exposed mice. Smoke exposure increased vertebral endplate porosity, which closely correlates with IDD in humans.
conclusionsThese findings further support tobacco smoke as a contributor to spinal degeneration. Furthermore, the data provide a novel mechanistic insight, indicating that smoking-induced IDD is a result of both reduced PG synthesis and increased degradation of a key disc extracellular matrix protein, aggrecan. Cleavage of aggrecan IGD is extremely detrimental as this results in the loss of the entire glycosaminoglycan-attachment region of aggrecan, which is vital for attracting water necessary to counteract compressive forces. Our results suggest identification and inhibition of specific metalloproteinases responsible for smoke-induced aggrecanolysis as a potential therapeutic strategy to treat IDD.
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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.