Related Experiment Video

Updated: Jun 1, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

The RANKL/RANK/OPG signaling pathway mediates medial arterial calcification in diabetic Charcot neuroarthropathy

Agbor Ndip1, Alfred Williams, Edward B Jude

  • 1Department of Medicine and Diabetes, Manchester Royal Infirmary, Manchester, UK. agbor.ako@manchester.ac.uk

Diabetes
|June 11, 2011
PubMed

Insights

The receptor activator of nuclear factor-κB (RANK) pathway is involved in vascular calcification in diabetic Charcot neuroarthropathy (CN). Targeting this pathway may offer new treatments for this condition.

Area of Science:

  • Vascular Biology
  • Endocrinology
  • Bone Metabolism

Background:

  • Diabetic Charcot neuroarthropathy (CN) is associated with osteolysis and medial arterial calcification (MAC).
  • The receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) pathway is implicated in bone metabolism but its role in MAC in CN is unclear.

Purpose of the Study:

  • To investigate the role of the RANKL/OPG signaling pathway in medial arterial calcification (MAC) in patients with diabetic Charcot neuroarthropathy (CN).

Main Methods:

  • Quantified serum cytokines including RANKL and OPG using ELISA and Bio-plex in patients with diabetes, CN, and healthy controls.
  • Immunohistochemical staining of human tibial artery segments for RANKL and Alizarin red.
  • In vitro studies using human vascular smooth muscle cells (VSMCs) exposed to patient sera and OPG.

Main Results:

  • RANKL expression was upregulated in areas of MAC.
  • Elevated systemic levels of RANKL, OPG, and inflammatory cytokines were observed in patients with CN.
  • CN serum accelerated VSMC osteoblastic differentiation and mineralization, which was inhibited by OPG and linked to nuclear factor-κB translocation.

Conclusions:

  • The RANKL/RANK/OPG signaling pathway is modulated in patients with CN and contributes to vascular calcification.
  • This pathway represents a potential therapeutic target for managing vascular complications in CN.
Abstract

More Related Videos

A Calcium Phosphate-Induced Mouse Abdominal Aortic Aneurysm Model05:14

A Calcium Phosphate-Induced Mouse Abdominal Aortic Aneurysm Model

Published on: November 18, 2022

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
Diabetic Neuropathy01:22

Diabetic Neuropathy

DefinitionDiabetic neuropathy is nerve damage caused by long-standing diabetes mellitus. It results directly from prolonged high blood sugar levels.PathophysiologyThe pathophysiology of diabetic neuropathy involves both metabolic and vascular disturbances triggered by chronic hyperglycemia.Metabolic injury: Elevated glucose levels activate the polyol pathway within nerve cells, leading to the accumulation of sorbitol and fructose. This increases oxidative stress, disrupts normal nerve...
Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation01:21

Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation

Clinical manifestationsPeripheral Arterial Disease (PAD) manifests through a range of symptoms, from the characteristic intermittent claudication to atypical presentations and severe complications in advanced stages. Intermittent claudication, a hallmark symptom of PAD, presents as exercise-induced muscle pain that typically resolves within minutes of rest. This pain is reproducible and stems from inadequate blood flow, leading to the accumulation of lactic acid produced during anaerobic...