Related Experiment Video

Updated: May 31, 2025

A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
05:46

A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.

Published on: February 14, 2021

3.6K

M2 macrophages regulate nucleus pulposus cell extracellular matrix synthesis through the OPN-CD44 axis in

Zhiwen Tao1, Tianyou Zhang1, Yaning Ge1

  • 1Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.

Osteoarthritis and Cartilage
|January 22, 2025
PubMed
Abstract

Insights

Macrophages influence intervertebral disc degeneration (IDD) by regulating nucleus pulposus cells (NPCs) extracellular matrix (ECM) expression via the osteopontin-CD44 axis. Targeting macrophages and this pathway offers therapeutic potential for IDD.

Area of Science:

  • Immunology
  • Orthopedics
  • Cell Biology

Background:

  • Macrophages are key immune cells involved in physiological processes.
  • Macrophage infiltration is observed in human intervertebral disc degeneration (IDD), but their specific role is unclear.

Purpose of the Study:

  • To investigate the role of macrophages in IDD.
  • To elucidate the mechanism by which macrophages influence nucleus pulposus cells (NPCs) and extracellular matrix (ECM) expression in IDD.
  • To explore the osteopontin-CD44 (OPN-CD44) axis in this process.

Main Methods:

  • Analysis of single-cell transcriptome data (GSE165722) to identify macrophage infiltration in IDD.
  • Verification of macrophage markers in human nucleus pulposus, lumbar spinal instability mice, and annulus fibrosus puncture mice.
  • In vitro co-culture of NPCs with M2 macrophages, treated with OPN neutralization antibody and siCD44.
  • In vivo experiments using OPN neutralization antibody and siCD44 treatments.
  • Investigation of the pSMAD2/3 pathway regulation by CD44.

Main Results:

  • IDD is characterized by macrophage infiltration and M2 polarization, particularly in the endplate.
  • Infiltrated macrophages express high levels of OPN, while NPCs upregulate CD44.
  • Macrophage depletion exacerbates IDD and reduces OPN and CD44 expression.
  • NPC-conditioned media induce M2 polarization of macrophages.
  • M2 macrophages restore NPC ECM phenotype via the OPN-CD44 axis by regulating pSMAD2/3 nuclear translocation.

Conclusions:

  • Macrophages regulate NPC ECM expression in IDD through the OPN-CD44 axis.
  • Targeting macrophages and the OPN-CD44 axis presents a promising therapeutic strategy for IDD prevention and treatment.
Keywords:
CD44CocultureIntervertebral disc degenerationMacrophageNucleus pulposus cellOPN

More Related Videos

Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration06:22

Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration

Published on: July 8, 2021

2.1K
Operational and Intervention Effects of Targeted Tuina in Lumbar Intervertebral Disc Degeneration Model Rabbits06:05

Operational and Intervention Effects of Targeted Tuina in Lumbar Intervertebral Disc Degeneration Model Rabbits

Published on: July 21, 2023

471

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.3K
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
8.8K
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
Extracellular Matrix01:26

Extracellular Matrix

Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
2.7K
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
2.5K