Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1

被引：15
作者：
Lu X. [1 ]
Xu G. [1 ]
Lin Z. [1 ]
Song J. [1 ]
Zhang Y. [1 ]
Wang H. [1 ]
Lu F. [1 ]
Xia X. [1 ]
Ma X. [1 ]
Zou F. [1 ]
Jiang J. [1 ]
机构：
[1] Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai
来源：
Oxidative Medicine and Cellular Longevity | 2023年 / 2023卷
关键词：
Antioxidants;
D O I：
10.1155/2023/3626091
中图分类号：
学科分类号：
摘要：
Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain, which brings heavy burdens to individuals and society. The mechanism of IVDD is complex and diverse. One of the important reasons is that the abnormal accumulation of reactive oxygen species (ROS) in nucleus pulposus cells (NPCs) leads to endoplasmic reticulum stress (ERS), which causes increased apoptosis of NPCs. Nuclear factor E2-related factor 2 (Nrf-2) and its downstream antioxidant proteins are key molecular switches for sensing oxidative stress and regulating antioxidant responses in cells. Sulforaphane (SFN), a natural compound derived from Brassicaceae plants, is a Nrf-2 agonist that displays potent antioxidant potential in vitro and in vivo. Here, we used advanced glycation end products (AGEs) to construct an in vitro degeneration model of NPCs, and we found that AGEs elevated ROS level in NPCs and caused severe ERS and apoptosis. While SFN can promote the entry of Nrf-2 into the nucleus and increase the expression level of heme oxygenase 1 (HO-1) in vitro, thus clearing the accumulated ROS in cells and alleviating ERS and cell apoptosis. Moreover, the protection of SFN on NPCs was greatly attenuated after HO-1 was inhibited. We also used AGEs to construct a rat IVDD model. Consistent with the in vitro experiments, SFN could attenuate ERS in NPCs in vivo and delay disc degeneration in rats. This study found that SFN can be used as a new and promising agent for the treatment of IVDD. © 2023 Xiao Lu et al.
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