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High cholesterol inhibits tendon-related gene expressions in tendon-derived stem cells through reactive oxygen

Kaiqun Li1, Ganming Deng1,2, Ye Deng1

  • 1Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Journal of Cellular Physiology
|March 3, 2019
PubMed

Insights

High cholesterol impairs tendon stem cell function by increasing oxidative stress and activating the NF-κB pathway, contributing to tendinopathy. This study elucidates a novel mechanism linking hypercholesterolemia to tendon injury.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Cell Biology

Background:

  • Clinical studies link high serum cholesterol to increased tendinopathy risk.
  • The specific impact of cholesterol on tendon-derived stem cells (TDSCs) and its mechanisms remain uninvestigated.

Purpose of the Study:

  • To investigate the association between cholesterol and tendinopathy in vitro and in vivo.
  • To elucidate the underlying molecular mechanisms of cholesterol-induced tendinopathy.

Main Methods:

  • Assessed cholesterol's effect on TDSCs using qPCR, Western blot, and immunofluorescence.
  • Measured intracellular reactive oxygen species (ROS) via flow cytometry.
  • Evaluated the NF-κB pathway using an IKK inhibitor (BAY 11-7082) and ROS scavenger (NAC).
  • Histologically analyzed Achilles tendons in apolipoprotein E mice on a high-fat diet.

Main Results:

  • High cholesterol reduced tendon cell marker expression (collagen 1, scleraxis, tenomodulin) and elevated ROS via NF-κB signaling in TDSCs.
  • NAC and BAY 11-7082 reversed cholesterol's inhibitory effects on TDSCs.
  • NAC inhibited cholesterol-induced phosphorylation of IκBα and p65.
  • Hypercholesterolemic mice exhibited significant Achilles tendon histological alterations.

Conclusions:

  • High cholesterol inhibits TDSC function and tendon-related gene expression through ROS-activated NF-κB signaling.
  • This pathway represents a novel mechanism underlying hypercholesterolemia-induced tendinopathy.
  • Findings suggest potential therapeutic targets for managing tendinopathy in hypercholesterolemic individuals.
Keywords:
NF-κB pathwayROScholesteroltendinopathytendon-derived stem cells

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