FGF21 inhibits the senescence of nucleus pulposus cells by activating mitophagy

This study employed third-generation RNA sequencing (RNA-seq) technology to analyze mRNA isolated from nucleus pulposus cell samples in the TBHP group (n=3) and the FGF21+TBHP intervention group (n=3). Pathway and network analysis based on Gene Ontology (GO) terms was conducted to identify the biological functions of differentially expressed mRNA. The results revealed that, based on the screening criteria for differentially expressed genes (|logFC|>1 and P<0.05), a total of 189 significantly differentially expressed genes (DEGs) were identified, including 100 significantly upregulated genes and 89 downregulated genes (Supplementary Table 1). The enriched functions of these differentially expressed genes were closely related to the cAMP signaling pathway, ion channels, and transport vesicles. Gene Set Enrichment Analysis (GSEA) indicated that these genes were closely associated with autophagy and selective autophagy. This study provides therapeutic targets and related pathways for FGF21 treatment of IDD, offering new insights and targets for medical or pharmacological intervention in IDD. Overall design: Nucleus pulposus cells (NPCs) were isolated from male Sprague-Dawley rats. Cells were cultured in vitro. Samples were divided into two experimental groups. The model group was treated with tert-butyl hydroperoxide (TBHP) to induce senescence. The treatment group was co-treated with TBHP and recombinant FGF21. Each group consisted of three biological replicates. Total RNA was extracted from these six samples. High-throughput RNA sequencing was performed to identify differentially expressed genes.