Related Experiment Video

Updated: Sep 20, 2025

Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
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Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis

Published on: November 28, 2015

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Notch/NICD/RBP-J signaling axis regulates M1 polarization of macrophages mediated by advanced glycation end products

Hao Tan1,2,3, Wenjie Xu1,2,3, Xiaoqian Ding1,2,3

  • 1Stomatological Hospital of Chongqing Medical University, Chongqing, China.

Glycoconjugate Journal
|June 6, 2022
PubMed

Insights

Advanced glycation end products (AGEs) drive M1 macrophage polarization and osteoclast formation, contributing to bone diseases. The Notch/NICD/RBP-J pathway is key to this AGEs-induced process.

Area of Science:

  • Biochemistry and Molecular Biology
  • Immunology
  • Bone Biology

Background:

  • Bone diseases like osteoporosis are linked to advanced glycation end products (AGEs) and macrophage polarization.
  • Understanding the mechanisms of AGEs in bone pathology is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of AGEs in macrophage polarization and osteoclastogenesis.
  • To elucidate the underlying molecular mechanisms, particularly the involvement of the Notch signaling pathway.

Main Methods:

  • RAW264.7 macrophages were treated with AGEs.
  • Analysis of M1 macrophage markers (nitric oxide, M1-associated genes, CD86).
  • Assessment of osteoclastogenesis and Notch pathway activation (NICD1 translocation).
  • Inhibition of Notch signaling using DAPT and RBP-J siRNA.

Main Results:

  • AGEs treatment increased M1 macrophage markers and osteoclastogenic potential.
  • AGEs activated the Notch signaling pathway, promoting NICD1 nuclear translocation.
  • Blocking Notch signaling (DAPT, RBP-J siRNA) reduced AGEs-induced M1 polarization.

Conclusions:

  • AGEs play a critical role in inducing M1 macrophage polarization and osteoclastogenesis.
  • The Notch/NICD/RBP-J signaling axis is essential for AGEs-mediated M1 polarization.
  • This study reveals a novel mechanism linking AGEs, macrophages, and bone disease progression.
Keywords:
Advanced glycation end products (AGEs)Macrophage polarizationNotch signalingOsteoclastogenesis

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