Related Experiment Video

Updated: Jun 2, 2025

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
07:51

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro

Published on: March 18, 2019

5.9K

Blocking the CCL5/CCL7-CCR1 axis regulates macrophage polarization through NF-κB pathway to alleviate the progression

Hanqing Xu1, Yi He2, Sheng Chen1

  • 1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan City, Hubei Province, China.

International Immunopharmacology
|January 13, 2025
PubMed
Abstract

Insights

Blocking the CCL5/CCL7-CCR1 axis reduces M1 macrophage polarization, mitigating osteoarthritis progression and synovitis by inhibiting the NF-κB pathway.

Area of Science:

  • Immunology
  • Rheumatology
  • Cell Biology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown.
  • Macrophage polarization plays a critical role in OA pathogenesis.
  • The chemokine receptor CCR1 and its ligands are implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the role of the CCR1 axis in macrophage polarization.
  • To evaluate the therapeutic potential of CCR1 inhibition in osteoarthritis.

Main Methods:

  • RAW macrophages were polarized to M1/M2 subtypes and treated with CCR1 inhibitor BX471.
  • Macrophage polarization was assessed using RT-qPCR, immunofluorescence, and flow cytometry.
  • In vivo studies utilized a DMM mouse model treated with BX471.

Main Results:

  • Inhibition of CCR1 and silencing of its ligands (CCL5, CCL7) decreased M1 macrophage polarization.
  • CCR1 blockade reduced NF-κB pathway activation and subsequent cartilage injury.
  • In vivo, CCR1 inhibition lessened M1 macrophage infiltration and alleviated articular cartilage damage.

Conclusions:

  • The CCL5/CCL7-CCR1 axis is a key regulator of macrophage polarization in OA.
  • Targeting this axis offers a potential therapeutic strategy to reduce synovitis and slow OA progression.
Keywords:
CCR1Macrophage polarizationOsteoarthritisSynovium

More Related Videos

Flow Cytometry Analysis of Immune Cell Subsets within the Murine Spleen, Bone Marrow, Lymph Nodes and Synovial Tissue in an Osteoarthritis Model12:23

Flow Cytometry Analysis of Immune Cell Subsets within the Murine Spleen, Bone Marrow, Lymph Nodes and Synovial Tissue in an Osteoarthritis Model

Published on: April 24, 2020

19.4K
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages10:07

Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages

Published on: June 23, 2013

66.1K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.2K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
946
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
1.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.6K
Inflammation01:38

Inflammation

Overview
52.5K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
2.8K