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

• Published in: The Journal of nutritional biochemistry 2021-10, Vol.96, p.108783-108783, Article 108783
• Main Authors: Sul, Ok-Joo, Li, Guoen, Kim, Ji-Eun, Kim, Eun-Sook, Choi, Hye-Seon
• Format: Article
• Language: English
• Subjects: 7-ketocholesterol; Animals; Autophagy; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Bone Resorption - metabolism; Ketocholesterols - metabolism; Male; Mice; Mice, Inbred C57BL; Osteoclast; Osteoclasts - cytology; Osteoclasts - metabolism; Oxidative Stress; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction; Transcription factor EB
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2021.108783

•Atherogenic diet increased 7-ketocholesterol (7-KC) in bone.•Bone resorption was associated with cholesterol and ROS in humans and mice.•7-KC increased the number and activity of OCs by enhancing autophagy.•7-KC enhanced autophagy via the ROS-TFEB signaling pathway. 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.