Spermidine promotes nucleus pulposus autophagy as a protective mechanism against apoptosis and ameliorates disc degeneration

Abstract

Spermidine has therapeutic effects in many diseases including as heart diastolic function, myopathic defects and neurodegenerative disorders via autophagy activation. Autophagy has been found to mitigate cell apoptosis in intervertebral disc degeneration (IDD). Accordingly, we theorize that spermidine may have beneficial effects on IDD via autophagy stimulation. In this study, spermidine's effect on IDD was evaluated in tert‐butyl hydroperoxide (TBHP)‐treated nucleus pulposus cells of SD rats in vitro as well as in a puncture‐induced rat IDD model. We found that autophagy was actuated by spermidine in nucleus pulposus cells. In addition, spermidine treatment weakened the apoptotic effects of TBHP in nucleus pulposus cells. Spermidine increased the expression of anabolic proteins including Collagen‐II and aggrecan and decreased the expression of catabolic proteins including MMP13 and Adamts‐5. Additionally, autophagy blockade using 3‐MA reversed the beneficial impact of spermidine against nucleus pulposus cell apoptosis. Autophagy was thus important for spermidine's therapeutic effect on IDD. Spermidine‐treated rats had an accentuated T2‐weighted signal and a diminished histological degenerative grade than vehicle‐treated rats, showing that spermidine inhibited intervertebral disc degeneration in vivo. Thus, spermidine protects nucleus pulposus cells against apoptosis through autophagy activation and improves disc, which may be beneficial for the treatment of IDD.

Parkin-mediated mitophagy as a potential therapeutic target for intervertebral disc degeneration

“…LBP is plaguing 80% of the world’s population and IDD was recognized as one of the major causes blame for LBP. It is widely accepted that apoptosis of NP cells contributes to the progression of IDD according to recent studies, including ours 29 – 32 . Inflammatory cytokines, especially TNF-α, were significantly elevated in NP tissues of the degenerated IVDs and accelerate the progression of IDD.…”

“…In recent studies, autophagy has been thought to be a protective mechanism under pathological conditions through degrading intracellular damaged proteins or dysfunctional organelles. According to studies from our group 30 – 32 as well as other groups 41 – 43 , autophagy plays an important role in protecting NP cells against apoptosis under pathological situation in vitro and postponing IDD process in vivo. Various drugs have been reported to induce selective mitochondria autophagy called mitophagy to eliminate the dysfunctional mitochondria.…”

Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway

“…Recent studies have proposed that spermidine can induce autophagy in several cellular models (Yang et al, ; Zheng et al, ). Thus, to determine whether stimulation with spermidine might promote autophagic flux in Ang II‐treated NRCs, protein expression of the autophagy‐associated molecules (LC3 II and p62) was evaluated after spermidine administration.…”

Long non‐coding RNA MALAT1 mediates hypoxia‐induced pro‐survival autophagy of endometrial stromal cells in endometriosis

“…Autophagy is vital in a range of pathophysiological situations, and dysregulated autophagy is associated with various human diseases, including neurodegenerative diseases, infection, and malignancy . It is generally believed that autophagy plays a crucial role in protecting cells to survival by preventing apoptosis under various metabolic stresses microenvironment, such as hypoxia or oxidative stress . Interestingly, our previous studies as well as others revealed that autophagic process was up‐regulated in ovarian endometriomas .…”