Abstract
BACKGROUND: Intervertebral disc degeneration (IDD) has the characteristics of global, high incidence and high disability rate, which brings a heavy economic and psychological burden to patients. Current clinical treatments are not effective in slowing the progression of IDD. Ferroptosis is an important cause of IDD development. The mechanism by which miR-188-5p regulates ferroptosis in nucleus pulposus cells (NPCs) has not been reported. METHODS: Firstly, bioinformatics was used to screen the miRNA and mRNA of differentially expressed genes in IDD. Then, clinical nucleus pulposus (NP) tissues were obtained for expression identification. TBHP induced ferroptosis in NPCs and detected the expression differences of miR-188-5p, P4HB and oxidative stress indicators, and verified the ability of transfection with miR-188-5p inhibitor to inhibit TBHP. Subsequently, the function of the miR-188-5p/P4HB axis was verified through experiments such as luciferase assay, cell transfection, and functional rescue. Finally, in vivo experiments were conducted to evaluate the ability of miR-188-5p to regulate IDD. RESULTS: Bioinformatics combined with a series of histological, cytological, and animal experiments revealed that miR-188-5p is an important ferroptosis driver in NPCs. MiR-188-5p accelerates IDD by mediating P4HB to regulate ferroptosis in NPCs. Finally, the rat IDD model confirmed that the miR-188-5p inhibitor significantly increased the height and signal intensity of the intervertebral space and inhibited intervertebral disc degeneration in rats. CONCLUSIONS: Collectively, our findings establish miR-188-5p as a ferroptosis driver in IDD. Knockdown of miR-188-5p significantly upregulated P4HB expression, suppressed ferroptosis, and attenuated IDD progression. This study identifies miR-188-5p as a potential therapeutic target, providing a novel mechanistic framework for IDD treatment strategies.