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High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem

Kaiqun Li1, Ye Deng1, Ganming Deng1,2

  • 1Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, China.

Stem Cell Research & Therapy
|March 22, 2020
PubMed
Abstract

Insights

High cholesterol triggers cell death and autophagy in tendon stem cells via ROS-activated AKT/FOXO1 signaling. This discovery offers new insights into how high cholesterol contributes to tendon injuries.

Area of Science:

  • Biomedical Science
  • Cell Biology
  • Molecular Biology

Background:

  • Hypercholesterolemia is a known risk factor for tendon pain and rupture.
  • Tendon-derived stem cells (TDSCs) are crucial in tendinopathy development.
  • Previous studies showed high cholesterol inhibits tendon-related gene expression in TDSCs.

Purpose of the Study:

  • To investigate the biological effects of high cholesterol on TDSCs.
  • To elucidate the molecular mechanisms underlying cholesterol-induced TDSC dysfunction.

Main Methods:

  • TDSCs were exposed to cholesterol (10 mg/dL) and assessed for apoptosis and autophagy.
  • Signaling pathways, including AKT/FOXO1 and reactive oxygen species (ROS), were analyzed.
  • Achilles tendons from hypercholesterolemic mice were examined histologically.

Main Results:

  • High cholesterol suppressed TDSC proliferation and migration, inducing cell cycle arrest.
  • Cholesterol simultaneously induced apoptosis and autophagy in TDSCs.
  • The ROS-activated AKT/FOXO1 pathway was identified as a key mediator of cholesterol-induced apoptosis and autophagy.

Conclusions:

  • High cholesterol induces apoptosis and autophagy in TDSCs via ROS-activated AKT/FOXO1 signaling.
  • This mechanism provides new insights into hypercholesterolemia-induced tendinopathy.
  • Targeting this pathway may offer therapeutic strategies for managing tendon disorders.
Keywords:
AKT/FOXO1 pathwayApoptosisAutophagyCholesterolROSTendinopathyTendon-derived stem cells

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