Acetylshikonin promoting PI3K/Akt pathway and inhibiting SOX4 expression to delay intervertebral disc degeneration and low back pain

Objective This study investigated the molecular mechanism by which acetylshikonin inhibits SOX4 expression via the PI3K/Akt pathway to delay intervertebral disc degeneration (IVDD) and low back pain (LBP). Method Bulk RNA-seq, RT-qPCR, Western blotting, immunohistochemical staining, small interfering RNA (siSOX4), lentivirus (lentiv-SOX4 hi ), and imaging techniques were used to assess SOX4 expression and validate its upstream regulatory pathway. Acetylshikonin and siSOX4 were injected into the IVD to measure IVDD. Result SOX4 expression significantly increased in degenerated IVD tissues. TNF-α increased SOX4 expression and apoptosis-related proteins in nucleus pulposus cells (NPCs). siSOX4 reduced TNF-α-induced NPCs apoptosis, while Lentiv-SOX4 hi increased it. The PI3K/Akt pathway was significantly correlated with SOX4, and acetylshikonin upregulated PI3K/Akt pathway while inhibiting SOX4 expression. In the anterior puncture IVDD mouse model, SOX4 expression was upregulated, and acetylshikonin and siSOX4 delayed IVDD-induced LBP. Conclusion Acetylshikonin delays IVDD-induced LBP by inhibiting SOX4 expression through the PI3K/Akt pathway. These findings offer potential therapeutic targets for future treatments. This article is protected by copyright. All rights reserved.