ArticleJOR spine2020
Advanced glycation end products cause RAGE-dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models.
Article in JOR spine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Musculoskeletal biomarkers in health and disease: implications for the aging spine-a review for spinal surgeons by the SRS adult spinal deformity task force on senescence.Spine deformity · 2025Review
- Degenerating intervertebral discs in the streptozotocin-high-fat diet model of type 2 diabetes show extensive inflammation.Disease models & mechanisms · 2025Article
- The transcriptome and secreted factors of the intervertebral discs in STZ-HFD Type 2 diabetic male mice reveal extensive inflammation.bioRxiv : the preprint server for biology · 2025Article
- Advanced Glycation End Products Induce Caudal Disc Degeneration in Ovariectomized Female Rats.JOR spine · 2025Article
- The RAGE Inhibitor TTP488 (Azeliragon) Improves Diabetic Bladder Dysfunction in Leptin-Deficient Obese Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Exploring the Causes of Intervertebral Disc Annulus Fibrosus Impairment.Cellular and molecular bioengineering · 2025Review
- Multi-omics analysis and evidence of IL1R1 as a potential biomarker for diabetes-associated intervertebral disc degeneration.Frontiers in immunology · 2025Article
- Regenerative potential of mouse neonatal intervertebral disc depends on collagen crosslink density.iScience · 2024Article
- Collagen integrity of the annulus fibrosus in degenerative disc disease individuals quantified with collagen hybridizing peptide.JOR spine · 2024Article
- Understanding the etiopathogenesis of lumbar intervertebral disc herniation: From clinical evidence to basic scientific research.JOR spine · 2024Review
- Article
- Peptide location fingerprinting identifies structural alterations within basement membrane components in ageing kidney.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Galectin-3 and RAGE differentially control advanced glycation endproduct-induced collagen damage in murine intervertebral disc organ culture.JOR spine · 2023Article
- The Chemistry and Biology of Collagen Hybridization.Journal of the American Chemical Society · 2023Review
- Review
- The degenerative impact of hyperglycemia on the structure and mechanics of developing murine intervertebral discs.JOR spine · 2022Article
- Role of Advanced Glycation End Products in Intervertebral Disc Degeneration: Mechanism and Therapeutic Potential.Oxidative medicine and cellular longevity · 2022Review
- Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human Organ.International journal of molecular sciences · 2021Article
- Diet-induced obesity leads to behavioral indicators of pain preceding structural joint damage in wild-type mice.Arthritis research & therapy · 2021Article
- Advanced Glycation End Product Inhibitor Pyridoxamine Attenuates IVD Degeneration in Type 2 Diabetic Rats.International journal of molecular sciences · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Aging and diabetes are associated with increased low-back pain and intervertebral disk (IVD) degeneration yet causal mechanisms remain uncertain. Advanced glycation end products (AGEs), which accumulate in IVDs from aging and are implicated in diabetes-related disorders, alter collagen and induce proinflammatory conditions. A need exists for methods that assess IVD collagen quality and degradation in order to better characterize specific structural changes in IVDs due to AGE accumulation and to identify roles for the receptor for AGEs (RAGE). We used multiphoton microscopy with second harmonic generation (SHG), collagen-hybridizing peptide (CHP), and image analysis methods to characterize effects of AGEs and RAGE on collagen quality and quantity in IVD annulus fibrosus (AF). First, we used SHG imaging on thin sections with an in vivo dietary mouse model and determined that high-AGE (H-AGE) diets increased AF fibril disruption and collagen degradation resulting in decreased total collagen content, suggesting an early degenerative cascade. Next, we used in situ SHG imaging with an ex vivo IVD organ culture model of AGE challenge on wild type and RAGE-knockout (RAGE-KO) mice and determined that early degenerative changes to collagen quality and degradation were RAGE dependent. We conclude that AGE accumulation leads to RAGE-dependent collagen disruption in the AF and can initiate molecular and tissue level collagen disruption. Furthermore, SHG and CHP analyzes were sensitive to collagenous alterations at multiple hierarchical levels due to AGE and may be useful in identifying additional contributors to collagen damage in IVD degeneration processes.
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