Related Experiment Video

Updated: Feb 6, 2026

Activating Autophagy by Aerobic Exercise in Mice
08:44

Activating Autophagy by Aerobic Exercise in Mice

Published on: February 3, 2017

12.8K

TFEB, a potential therapeutic target for osteoarthritis via autophagy regulation

Gang Zheng1,2, Yu Zhan3, Xiaobin Li1,2

  • 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.

Cell Death & Disease
|August 30, 2018
PubMed

Insights

Transcription factor EB (TFEB) activity decreases in osteoarthritis (OA). Upregulating TFEB in chondrocytes protects against OA development by enhancing autophagic flux and reducing cell death, suggesting TFEB as a potential OA therapeutic target.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Osteoarthritis Research

Background:

  • Autophagic flux blockage in chondrocytes contributes to osteoarthritis (OA) pathogenesis, leading to apoptosis and senescence.
  • The precise molecular mechanisms and therapeutic interventions for impaired autophagic flux in OA remain unclear.
  • Transcription factor EB (TFEB) has emerged as a master regulator of autophagy and lysosomal biogenesis.

Purpose of the Study:

  • To investigate the role of TFEB expression and activity in OA development.
  • To evaluate the therapeutic potential of TFEB upregulation for OA treatment.
  • To determine the effect of TFEB on autophagic flux and chondrocyte protection in OA models.

Main Methods:

  • Assessed TFEB expression and nuclear localization in human and mouse OA cartilage and in vitro chondrocyte models.
  • Utilized lentivirus-mediated TFEB overexpression in chondrocytes exposed to tert-Butyl hydroperoxide (TBHP).
  • Employed a destabilized medial meniscus (DMM) mouse model to study TFEB effects in vivo.

Main Results:

  • TFEB expression and nuclear localization were reduced in OA cartilage and TBHP-treated chondrocytes.
  • TFEB overexpression in chondrocytes restored autophagic flux, improved lysosome function, and protected against TBHP-induced apoptosis and senescence.
  • In the DMM mouse model, TFEB overexpression alleviated cartilage degradation, reduced chondrocyte apoptosis/senescence, and enhanced autophagic flux.

Conclusions:

  • Chondrocyte TFEB activity is implicated in the development of osteoarthritis.
  • TFEB overexpression demonstrates protective effects against OA-associated cellular damage.
  • Upregulating TFEB presents a promising therapeutic strategy for osteoarthritis treatment.

More Related Videos

Use of Shigella flexneri to Study Autophagy-Cytoskeleton Interactions12:52

Use of Shigella flexneri to Study Autophagy-Cytoskeleton Interactions

Published on: September 9, 2014

16.4K
Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

1.5K

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.9K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Regulated mRNA Transport02:22

Regulated mRNA Transport

In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
7.0K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.8K
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
136.4K
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
9.9K