ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2019
High mobility group box-1 induces pro-inflammatory signaling in human nucleus pulposus cells via toll-like receptor 4-dependent pathway.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- HMGB1 Mediates Macrophage Recruitment and Regional Intervertebral Disc Properties Following Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- ROS anchor PAMPs-mediated extracellular HMGB1 self-association and its dimerization enhances pro-inflammatory signaling.Redox biology · 2025Article
- Multi-Cohort Transcriptomic Profiling of Medical Gas Plasma-Treated Cancers Reveals the Role of Immunogenic Cell Death.Cancers · 2024Article
- Sex differences in the biomechanical and biochemical responses of caudal rat intervertebral discs to injury.JOR spine · 2023Article
- Amentoflavone attenuates oxidative stress and neuroinflammation induced by cerebral ischemia/reperfusion in rats by targeting HMGB1-mediated TLR4/NF-κB signaling pathway.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs.Biomolecules · 2023Article
- Chronic Pain at Multiple Sites Increases Myocardial Infarction: If So, Why?JACC. Advances · 2023Article
- Blocking toll-like receptor 4 mitigates static loading induced pro-inflammatory expression in intervertebral disc motion segments.Journal of biomechanics · 2023Article
- Clinical Biomarker of Sterile Inflammation, HMGB1, in Patients with Chronic Non-Specific Low Back Pain: A Pilot Cross-Sectional Study.Life (Basel, Switzerland) · 2023Article
- STING signaling in inflammaging: a new target against musculoskeletal diseases.Frontiers in immunology · 2023Review
- Article
- Degenerative Disc Disease of the Spine: From Anatomy to Pathophysiology and Radiological Appearance, with Morphological and Functional Considerations.Journal of personalized medicine · 2022Review
- Expression of adipokines and adipocytokines by epidural adipose tissue in cauda equina syndrome in dogs.Journal of veterinary internal medicine · 2022Article
- Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation.International journal of molecular sciences · 2022Review
- High-mobility group box 1 (HMGB1) in COVID-19: extrapolation of dangerous liaisons.Inflammopharmacology · 2022Review
- An in vitro 3D annulus fibrosus cell culture model with type I collagen: An examination of cell-matrix interactions.JOR spine · 2022Article
- The Potential Role of Polyphenols in Oxidative Stress and Inflammation Induced by Gut Microbiota in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway.Bone & joint research · 2021Article
- Association between high mobility group box 1 protein and juvenile idiopathic arthritis: a prospective longitudinal study.Pediatric rheumatology online journal · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Intervertebral disc (IVD) degeneration (DD) is associated with low back pain, the leading cause of disability worldwide. Damage-associated molecular patterns (DAMPs) that contribute to inflammation and trigger DD have not been well characterized. Extracellular high mobility group box-1 (HMGB1) protein has been implicated as a potent DAMP and pro-inflammatory stimulus in the immune system. In this study, we show that HMGB1 and IL-6 levels increase in patients with advanced DD in comparison to early DD. This study further tested the hypothesis that HMGB1 promotes inflammatory signaling driving DD in human nucleus pulposus (NP) cells and tissue. Immunofluorescence and western blot analysis confirmed the expression of HMGB1 and its extracellular release by NP cells under cell stress. Gene expression and protein quantification indicate that HMGB1 stimulates the expression IL-6 and MMP-1 in a dose-dependent manner. The contributions of toll-like receptor (TLR) -2, -4 and receptor for advanced glycation end products (RAGE) as receptors mediating HMGB1 signaling was examined using small molecule inhibitors. Inhibition of TLR-4 signaling, with TAK-242, completely abrogated HMGB1 induced IL-6 and MMP-1 expression, whereas inhibition of TLR-2, with O-vanillin, or RAGE, with FPS-ZM1, had mild inhibitory effects. HMGB1 stimulation activated NF-ĸB signaling while TAK-242 co-treatment abrogated it. Lastly, effects of HMGB1 on matrix deposition was evaluated in a 3D culture system of human NP cells. These results implicate HMGB1 as a potent DAMP that promotes inflammation in NP cells and degradation of NP tissues. TLR4-HMGB1 axis is a potential major pathway to alleviate disc inflammation and mitigate DD. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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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.