Abstract
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.
Highlights
As an age-related degenerative disease, intervertebral disc degeneration (IDD) has been widely perceived as the main cause of low back pain that occurs in all age groups, bringing about great social and economic burdens [1, 2]
Based on findings that Kinsenoside could exert multiple pharmacological effects, we found that Kinsenoside rescued the nucleus pulposus cells (NPCs) viability under oxidative stress and protected against apoptosis, senescence and mitochondrial dysfunction in a nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent way
Increasing studies have demonstrated that the accumulation of oxidation products in nucleus pulposus (NP) tissues forms a microenvironment of oxidative stress and contributes to the progression of Intervertebral disc degeneration (IDD) [31,32,33]
Summary
As an age-related degenerative disease, intervertebral disc degeneration (IDD) has been widely perceived as the main cause of low back pain that occurs in all age groups, bringing about great social and economic burdens [1, 2]. A normal intervertebral disc (IVD) consists of an outer annulus fibrosus (AF) that forms a ring structure to enclose the central nucleus pulposus (NP) and is connected to adjacent vertebral bodies by the cartilaginous endplates. The molecular mechanism of these pathological changes has not been fully understood, the apoptosis and senescence of NPCs are proven to be crucial to the development of IDD [8,9,10]. Mitochondrial dysfunction is regarded as an important factor in NPC apoptosis and senescence, and accelerates disc degeneration [14,15,16].
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