ArticleDiabetes2011
The RANKL/RANK/OPG signaling pathway mediates medial arterial calcification in diabetic Charcot neuroarthropathy.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Association between Osteoprotegerin and Charcot Neuroarthropathy: a systematic review.Acta diabetologica · 2021Pooled it
- GLP-1 receptor agonists vs DPP-4 inhibitors and neuropathic complications in type 2 diabetes.Journal of neurology · 2026Article
- Diabetic Charcot Neuroarthropathy: A Contemporary Review of Molecular and Genetic Markers.Foot & ankle international · 2026Review
- Peripheral Arterial Disease in Diabetic Foot: One Disease with Multiple Patterns.Journal of clinical medicine · 2025Review
- PATHOGENESIS OF ACUTE DIABETIC CHARCOT ARTHROPATHY IN THE FOOT AND ANKLE: A COMPREHENSIVE LITERATURE REVIEW.Orthopedic reviews · 2025Article
- Article
- Charcot neuro-osteoarthropathy: a review of key concepts and an evidence-based surgical management algorithm.Frontiers in clinical diabetes and healthcare · 2024Review
- The role of miR-433-3p in vascular calcification in type 2 diabetic patients: targeting WNT/β-Catenin and RANKL/RANK/OPG signaling pathways.Molecular biology reports · 2023Article
- Association of rs2073618 polymorphism and osteoprotegerin levels with hypertension and cardiovascular risks in patients with type 2 diabetes mellitus.Scientific reports · 2023Article
- Evaluating Classification Systems of Diabetic Foot Ulcer Severity: A 12-Year Retrospective Study on Factors Impacting Survival.Healthcare (Basel, Switzerland) · 2023Article
- Biomarkers for Prostate Cancer Bone Metastasis Detection and Prediction.Journal of personalized medicine · 2023Review
- Therapeutics of Charcot neuroarthropathy and pharmacological mechanisms: A bone metabolism perspective.Frontiers in pharmacology · 2023Review
- Roles of osteoprotegerin in endocrine and metabolic disorders through receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B signaling.Frontiers in cell and developmental biology · 2022Review
- Pathophysiology and Molecular Imaging of Diabetic Foot Infections.International journal of molecular sciences · 2021Review
- Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling.Current issues in molecular biology · 2021Article
- Loss of SIRT1 in diabetes accelerates DNA damage-induced vascular calcification.Cardiovascular research · 2021Article
- Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study.Cardiovascular diabetology · 2020Observational
- Mechanisms of the Osteogenic Switch of Smooth Muscle Cells in Vascular Calcification: WNT Signaling, BMPs, Mechanotransduction, and EndMT.Bioengineering (Basel, Switzerland) · 2020Review
- Ginsenoside Rb1 ameliorates CKD-associated vascular calcification by inhibiting the Wnt/β-catenin pathway.Journal of cellular and molecular medicine · 2019Article
- Effect of Bushen Huoxue decoction on inhibiting osteogenic differentiation of vascular smooth cells by regulating OPG/RANK/RANKL system in vascular calcification.Annals of translational medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) signaling pathway (RANKL/RANK/OPG signaling) is implicated in the osteolysis associated with diabetic Charcot neuroarthropathy (CN); however, the links with medial arterial calcification (MAC) seen in people with CN are unclear. This study aimed to investigate the role of RANKL/OPG in MAC in patients with CN. RESEARCH DESIGN AND
methodsEnzyme-linked immunosorbent assay and Bio-plex multiarray technology were used to quantify a range of cytokines, including RANKL and OPG in sera from 10 patients with diabetes, 12 patients with CN, and 5 healthy volunteers. Human tibial artery segments were immunohistochemically stained with Alizarin red and human RANKL antibody. Human vascular smooth muscle cells (VSMCs) were also explanted from arterial segments for in vitro studies.
resultsWe demonstrate colocalization and upregulation of RANKL expression in areas displaying MAC. Systemic levels of RANKL, OPG, and inflammatory cytokines (interleukin-8, granulocyte colony-stimulating factor) were elevated in those with CN compared with diabetic patients and healthy control subjects. Human VSMCs cultured in CN serum showed accelerated osteoblastic differentiation (alkaline phosphatase activity) and mineralization (alizarin red staining) compared with cells treated with diabetic or control serum (P < 0.05). Coincubation with OPG, the decoy receptor for RANKL, attenuated osteogenic differentiation of VSMCs and was independent of a high calcium-phosphate milieu. The accelerated mineralization induced by RANKL and CN serum correlated with nuclear translocation of nuclear factor-κB, a process abrogated by OPG.
conclusionsOur data provide direct evidence that RANKL/RANK/OPG signaling is modulated in patients with CN and plays a role in vascular calcification. This study highlights this pathway as a potential target for intervention.
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