Research Paper Volume 11, Issue 18 pp 7961—7977
Kinsenoside ameliorates intervertebral disc degeneration through the activation of AKT-ERK1/2-Nrf2 signaling pathway
- 1 Department of Orthopedics, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China
- 2 Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing 400038, China
Received: July 25, 2019 Accepted: September 15, 2019 Published: September 23, 2019https://doi.org/10.18632/aging.102302
How to Cite
Copyright © 2019 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Intervertebral disc degeneration (IDD) is recognized as the major contributor to low back pain, which results in disability worldwide and heavy burdens on society and economy. Here we present evidence that the lower level of Nrf2 is closely associated with higher grade of IDD. The apoptosis and senescence of nucleus pulposus cells (NPCs) were exacerbated by Nrf2 knockdown, but suppressed by Nrf2 overexpression under oxidative stress. Based on findings that Kinsenoside could exert multiple pharmacological effects, we found that Kinsenoside rescued the NPC viability under oxidative stress and protected against apoptosis, senescence and mitochondrial dysfunction in a Nrf2-dependent way. Further experiments revealed that Kinsenoside activated a signaling pathway of AKT-ERK1/2-Nrf2 in NPCs. Moreover, in vivo study showed that Kinsenoside ameliorated IDD in a puncture-induced model. Together, the present work suggests that Nrf2 is involved in the pathogenesis of IDD and shows the protective effects as well as the underlying mechanism of Kinsenoside on Nrf2 activation in NPCs.