7-ketocholesterol enhances autophagy via the ROS-TFEB signaling pathway in osteoclasts

J Nutr Biochem. 2021 Oct:96:108783. doi: 10.1016/j.jnutbio.2021.108783. Epub 2021 May 21.

Abstract

Oxysterols play a critical role in human health and diseases associated with high cholesterol and oxidative stress. Given that a positive correlation was observed between cholesterol and collagen type 1 fragment (CTX-1) or serum reactive oxygen species (ROS) in humans, we hypothesized that oxidized cholesterol metabolites may participate in cholesterol-induced bone loss. Therefore, this study aimed to identify the metabolite responsible for cholesterol-associated bone loss and evaluate its effect on osteoclasts (OCs) leading to bone loss. An atherogenic diet in mice increased the levels of the oxysterol, 7-ketocholesterol (7-KC) in bone, as well as serum ROS. 7-KC increased the number and activity of OCs by enhancing autophagy via the ROS-transcription factor EB signaling pathway. These findings suggest that 7-KC acts as a cholesterol metabolite and is at least partially responsible for cholesterol-induced bone loss by inducing autophagy in OCs.

Keywords: 7-ketocholesterol; Osteoclast; Reactive oxygen species; Transcription factor EB; autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Bone Resorption / metabolism
  • Ketocholesterols / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Ketocholesterols
  • Reactive Oxygen Species
  • Tcfeb protein, mouse
  • 7-ketocholesterol