Related Experiment Video

Updated: Jul 26, 2025

Author Spotlight: Insight Into Advances in Prion Diseases Research
10:40

Author Spotlight: Insight Into Advances in Prion Diseases Research

Published on: August 11, 2023

521

Glucocorticoid-induced activation of NOX/ROS/NF-κB signaling in MSCs contributes to the development of GONFH

Huihui Xu1,2,3, Qinghe Zeng1,2,3, Kaiao Zou1,2,3

  • 1The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China.

Apoptosis : an International Journal on Programmed Cell Death
|June 12, 2023
PubMed
Abstract

Insights

Glucocorticoids (GCs) induce femoral head osteonecrosis by promoting oxidative stress in mesenchymal stem cells (MSCs). This pathway, involving NOX/ROS/NF-κB, leads to cell death and differentiation imbalance, contributing to GONFH pathogenesis.

Area of Science:

  • Biomedical research
  • Cell biology
  • Pathogenesis studies

Background:

  • Glucocorticoids (GCs) are associated with osteonecrosis of the femoral head (GONFH).
  • The precise mechanisms underlying GC-induced GONFH require further elucidation.
  • Understanding the role of mesenchymal stem cells (MSCs) in this process is critical.

Purpose of the Study:

  • To investigate the pathogenic factors and underlying mechanisms of glucocorticoids (GCs)-induced osteonecrosis of the femoral head (GONFH).
  • To explore the role of oxidative stress and MSCs in GC-induced bone damage.
  • To identify potential therapeutic targets for GONFH.

Main Methods:

  • In vivo and in vitro studies using GONFH patients and rat models.
  • Utilized techniques including µCT scanning, histopathology, immunohistochemistry, ROS and TUNEL staining.
  • Employed flow cytometry, gene expression (RT-qPCR), and protein analysis (Western blotting) to assess cellular mechanisms.

Main Results:

  • GCs significantly increased reactive oxygen species (ROS) and aggravated oxidative stress (OS) in MSCs.
  • GCs promoted MSC apoptosis and an imbalance in osteogenic/lipogenic differentiation.
  • NOX family proteins were identified as key mediators of ROS production by GCs.

Conclusions:

  • GCs induce GONFH by promoting an OS microenvironment in MSCs via the NOX/ROS/NF-κB pathway.
  • This leads to MSC apoptosis and impaired differentiation, crucial factors in GONFH pathogenesis.
  • Inhibitors of NOX and NF-κB show potential in ameliorating GC-induced MSC damage.
Keywords:
ApoptosisDifferentiationGONFHMesenchymal stem cellOxidative stress

More Related Videos

ROS Live Cell Imaging During Neuronal Development09:25

ROS Live Cell Imaging During Neuronal Development

Published on: February 9, 2021

4.3K
Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models10:42

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models

Published on: October 22, 2012

16.3K

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...
7.5K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K
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...
1.1K
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
4.8K
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...
9.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K