Abstract
The death of nucleus pulposus (NP) cells is an important cause of intervertebral disc (IVD) degeneration. Redox disturbance caused by dysfunctional mitochondria has been considered as a vital risk for NP cell survival. It is valuable to identify key proteins maintaining mitochondrial function in NP cells. A previous study found that regulated in development and DNA damage response 1 (REDD1) are upregulated during intervertebral disc degeneration and that REDD1 can cause NP cell apoptosis. Thus, the present study further explores the effect of REDD1 on IVD degeneration. Our results showed that REDD1 promotes NP cell apoptosis via the mitochondrial pathway. Importantly, REDD1 formed a complex with TXNIP to strengthen its own action, and the combination was consolidated under H2O2-induced oxidative stress. The combined inhibition of the REDD1/TXNIP complex was better than that of REDD1 or TXNIP alone in restoring cell proliferation and accelerating apoptosis. Moreover, p53 acts as the transcription factor of REDD1 to regulate the REDD1/TXNIP complex under oxidative stress. Altogether, our results demonstrated that the REDD1/TXNIP complex mediated H2O2-induced human NP cell apoptosis and IVD degeneration through the mitochondrial pathway. Interferences on these sites to achieve mitochondrial redox homeostasis may be a novel therapeutic strategy for oxidative stress-associated IVD degeneration.
Highlights
Low back pain (LBP) is one of the most critical causes of disability around the world which has contributed to large economic and social costs [1, 2]
Our recent study has showed that REDD1 expression was increased with the progression of intervertebral disc (IVD) degeneration, and REDD1 deletion could dwindle serum deprivation-induced nucleus pulposus (NP) cell apoptosis [20]
Our previous work has proven that REDD1 was highly expressed in IVD degeneration and accelerated this progress [20]
Summary
Low back pain (LBP) is one of the most critical causes of disability around the world which has contributed to large economic and social costs [1, 2]. It is reported that up to 80% of people will suffer from LBP during their lifetime [3]. Many factors associated with LBP have been found. Degeneration of the intervertebral disc (IVD) is one major cause [4, 5]. There is plenty of research done in relation to IVD and LBP, the pathogenesis of IVD degeneration is not fully defined. As the important intermediate metabolite, reactive oxygen species (ROS) has been proven to be a key mediator during the occurrence and progression of IVD degeneration. The balance is between ROS generation and scavenging control
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