ArticleEuropean cells & materials2016
AGEs induce ectopic endochondral ossification in intervertebral discs
Article in European cells & materials, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Elucidation of Baicalein's Anti-Intervertebral Disc Degeneration Mechanism Through Network Pharmacology and Experimental Validation.Cell biochemistry and biophysics · 2026Article
- Exploring the relationship between gut microbiota and spinal canal stenosis: a bidirectional Mendelian randomization and hub gene study across East Asian and European populations.Asian spine journal · 2026Article
- Identification and validation of NETs-associated biomarkers in osteoporosis with diabetes.Scientific reports · 2026Article
- Cellular and molecular mechanisms of diabetes-mediated disc degeneration.Frontiers in endocrinology · 2026Review
- Characterization of bone & cartilage endplate junction in the human lumbar spine: novel ultrastructural insights & association with elemental composition, vascularity and degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025Article
- Oral Citrate Supplementation Mitigates Age-Associated Pathologic Intervertebral Disc Calcification in LG/J Mice.Aging cell · 2025Article
- A spontaneous anterior fusion of lumbar spine after posterolateral lumbar fusion with pedicle screw-plate system.BMC musculoskeletal disorders · 2025Article
- Role of macrophage in intervertebral disc degeneration.Bone research · 2025Review
- Elemental imbalance and oxidative biomarker shifts in lumbar disc degeneration.Frontiers in neurology · 2025Article
- Oral citrate supplementation mitigates age-associated pathological intervertebral disc calcification in LG/J mice.bioRxiv : the preprint server for biology · 2024Article
- Transcriptional profiling of human cartilage endplate cells identifies novel genes and cell clusters underlying degenerated and non-degenerated phenotypes.Arthritis research & therapy · 2024Article
- Roles of organokines in intervertebral disc homeostasis and degeneration.Frontiers in endocrinology · 2024Review
- Network Pharmacology with Metabolomics Study to Reveal the Mechanisms of Bushen Huoxue Formula in Intervertebral Disc Degeneration Treatment.Drug design, development and therapy · 2024Article
- ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells.BMC musculoskeletal disorders · 2023Article
- ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models.Journal of inflammation research · 2023Article
- Intervertebral disc degeneration-Current therapeutic options and challenges.Frontiers in public health · 2023Review
- The Potential Role of Cytokines in Diabetic Intervertebral Disc Degeneration.Aging and disease · 2022Article
- Changes in Elements and Relationships among Elements in Intervertebral Disc Degeneration.International journal of environmental research and public health · 2022Article
- Mechanisms and clinical implications of intervertebral disc calcification.Nature reviews. Rheumatology · 2022Review
- Herbal Formula Modified Bu-Shen-Huo-Xue Decoction Attenuates Intervertebral Disc Degeneration via Regulating Inflammation and Oxidative Stress.Evidence-based complementary and alternative medicine : eCAM · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ectopic calcifications in intervertebral discs (IVDs) are known characteristics of IVD degeneration that are not commonly reported but may be implicated in structural failure and dysfunctional IVD cell metabolic responses. This study investigated the novel hypothesis that ectopic calcifications in the IVD are associated with advanced glycation end products (AGEs) via hypertrophy and osteogenic differentiation. Histological analyses of human IVDs from several degeneration stages revealed areas of ectopic calcification within the nucleus pulposus and at the cartilage endplate. These ectopic calcifications were associated with cells positive for the AGE methylglyoxal-hydroimidazolone-1 (MG-H1). MG-H1 was also co-localised with Collagen 10 (COL10) and Osteopontin (OPN) suggesting osteogenic differentiation. Bovine nucleus pulposus and cartilaginous endplate cells in cell culture demonstrated that 200 mg/mL AGEs in low-glucose media increased ectopic calcifications after 4 d in culture and significantly increased COL10 and OPN expression. The receptor for AGE (RAGE) was involved in this differentiation process since its inhibition reduced COL10 and OPN expression. We conclude that AGE accumulation is associated with endochondral ossification in IVDs and likely acts via the AGE/RAGE axis to induce hypertrophy and osteogenic differentiation in IVD cells. We postulate that this ectopic calcification may play an important role in accelerated IVD degeneration including the initiation of structural defects. Since orally administered AGE and RAGE inhibitors are available, future investigations on AGE/RAGE and endochondral ossification may be a promising direction for developing non-invasive treatment against progression of IVD degeneration.
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Registered trials
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