Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells

Abstract

Oxidative stress–induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)–induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.

Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration

“…Following transfection with siRNA-TFEB, apigenin failed to inhibit the senescence of NP cells induced by THBP. 96 What's more, Wang et al 97 reported that parathyroid hormone 1-34 (PTH) could inhibit the mTOR signalling pathway, promote autophagy in rat NP cells, and suppress NP cell senescence; transfection of siRNA-ATG5 inhibited autophagy, and the protective effect of PTH was abolished. These studies suggest that inhibition of the mTOR pathway might suppress NP cell senescence.…”

Mesenchymal Stem Cells May Alleviate the Intervertebral Disc Degeneration by Reducing the Oxidative Stress in Nucleus Pulposus Cells

“…The autophagy level was higher in degenerative NPCs compared with normal NPCs, which indicated that autophagy might be involved in the deterioration of IDD [55]. Many investigations have indicated that autophagy was an important protective factor for IVD, and the restoration of autophagy was a promising research direction in IDD [13,[56][57][58]. Some studies have indicated that MSCs could significantly increase the autophagy level, and reduce the apoptosis of NPCs [25,59].…”

Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities

“…Mechanistically, circKIF18A suppressed the proteasomal degradation of mini-chromosome maintenance complex component 7 (MCM7) [ 39 ]. In addition, other exogenous oxidative stressors such as tert-butyl hydroperoxide (TBHP) are widely used in NP cells to induce premature CS signaling in cultured cells [ 43 , 44 , 45 ]. The DNA damage caused by oxidative stress is sensed by the stimulator of interferon genes (STING) pathway to regulate senescence in NP cells [ 46 ].…”