Electroacupuncture regulates SIRT1/p53/p21 signaling pathway to prevent stress-induced premature senescence of nucleus pulposus cells in degenerative intervertebral discs

Abstract

Stress-induced premature senescence (SIPS) affects cellular functionality due to various stressors. In intervertebral disc degeneration (IVDD), nucleus pulposus (NP) cell dysfunction is crucial. Electroacupuncture (EA) has been used to alleviate low back pain and delay IVDD, but its potential mechanism is not yet well understood. The research was to explore EA's effect on SIPS in NP cells of degenerated intervertebral discs. Rabbits were subjected to axial compression for 28 days, and the modeling results were evaluated by Magnetic Resonance Imaging (MRI). After successful modeling, EA intervention was applied to the "Jiaji" acupoints (EX-B2) in the waist for 28 days. The comprehensive reaction scores of experimental rabbits, together with apoptosis, inflammation, and SIPS of NP cells were observed. Adeno-associated virus SIRT1-RNAi and p53 inhibitor Pifithrin-α (PFTα) were injected into degenerated intervertebral discs to reduce SIRT1 and p53 expressions, and the SIPS of NP cells was observed. The results showed that EA was effective in enhancing the comprehensive reaction ability of rabbits, improving the morphological structure of NP cells, inhibiting NP apoptosis, reducing inflammatory reactions, and delaying NP cell SIPS. Low expression of SIRT1 enhanced SIPS in NP cells, and EA inhibited the p53/p21 signaling pathway. In addition, EA could delay SIPS in NP cells by modulating the p53/p21 signaling pathway through SIRT1. This investigation provides original perspectives on the efficacy of EA as a modality for delaying IVDD. Nevertheless, additional research is warranted to firmly establish EA as a viable treatment for IVDD.

Keywords: Electroacupuncture; Intervertebral disc; Intervertebral disc degeneration; Nucleus pulposus cell; Senescence; Silent information regulator 1.