Related Experiment Video

Updated: Oct 23, 2025

Real-time Visualization and Analysis of Chondrocyte Injury Due to Mechanical Loading in Fully Intact Murine Cartilage Explants
08:42

Real-time Visualization and Analysis of Chondrocyte Injury Due to Mechanical Loading in Fully Intact Murine Cartilage Explants

Published on: January 7, 2019

7.0K

TGFβ1 signaling protects chondrocytes against oxidative stress via FOXO1-autophagy axis

I Kurakazu1, Y Akasaki1, H Tsushima1

  • 1Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka city, Fukuoka, 812-8582, Japan.

Osteoarthritis and Cartilage
|August 22, 2021
PubMed
Abstract

Insights

Transforming growth factor β1 (TGFβ1) protects chondrocytes from oxidative stress by regulating the forkhead box O1 (FOXO1) and autophagy pathway. Reduced ALK5 expression with aging may decrease FOXO1 levels, contributing to osteoarthritis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The transcription factor forkhead box O1 (FOXO1) is crucial for autophagy, a cellular process that declines with age.
  • Reduced FOXO1 expression in chondrocytes is linked to osteoarthritis development due to impaired autophagy.
  • The precise mechanisms regulating FOXO1 expression and its age-related decline remain largely unknown.

Purpose of the Study:

  • To elucidate how transforming growth factor β1 (TGFβ1) signaling influences the FOXO1-autophagy axis in chondrocytes.
  • To investigate the role of TGFβ1 in chondrocyte protection against oxidative stress.

Main Methods:

  • Chondrocyte cultures were treated with TGFβ1, and FOXO1 expression was analyzed.
  • Immunohistochemistry assessed activin receptor-like kinase 5 (ALK5) and FOXO1 levels in mouse knee joints across different age groups.
  • Experiments involved ALK5 inhibition, SMAD2/3 knockdown, and hydrogen peroxide (H2O2) treatment to evaluate TGFβ1's effects on autophagy and cell survival.

Main Results:

  • TGFβ1 significantly increased both FOXO1 mRNA and protein expression.
  • Expression of ALK5 and FOXO1 diminished with increasing age in mice.
  • TGFβ1 enhanced autophagy marker LC3-II expression via the SMAD3-FOXO1 pathway and protected chondrocytes from H2O2-induced cell death, an effect dependent on FOXO1.

Conclusions:

  • TGFβ1 confers chondrocyte protection against oxidative stress by activating the FOXO1-mediated autophagy pathway.
  • A decrease in ALK5 expression during aging may underlie the reduction in FOXO1 expression, potentially contributing to osteoarthritis pathogenesis.
Keywords:
Activin receptor-like kinase 5AutophagyForkhead box O1Oxidative stressTransforming growth factor β1

More Related Videos

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness08:52

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness

Published on: March 18, 2022

3.2K
Chondrogenic Differentiation Induction of Adipose-derived Stem Cells by Centrifugal Gravity08:30

Chondrogenic Differentiation Induction of Adipose-derived Stem Cells by Centrifugal Gravity

Published on: February 24, 2017

9.7K

Related Concept Videos

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...
8.0K
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...
8.0K
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
779