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.

氧甾醇在人类健康以及与高胆固醇和氧化应激相关的疾病中发挥着至关重要的作用。鉴于在人类中观察到胆固醇与 1 型胶原片段 (CTX-1) 或血清活性氧 (ROS) 之间呈正相关，我们假设氧化胆固醇代谢物可能参与胆固醇诱导的骨质流失。因此，本研究旨在确定导致胆固醇相关骨质流失的代谢物，并评估其对导致骨质流失的破骨细胞 (OC) 的影响。小鼠的致动脉粥样硬化饮食增加了骨中氧甾醇、7-酮胆固醇 (7-KC) 以及血清 ROS 的水平。 7-KC 通过 ROS 转录因子 EB 信号通路增强自噬，从而增加 OC 的数量和活性。这些发现表明，7-KC 作为一种胆固醇代谢物，通过诱导 OC 中的自噬，至少部分地导致胆固醇诱导的骨质流失。