Advanced glycation end products induce nucleus pulposus cell apoptosis by upregulating TXNIP via inhibiting glycolysis pathway in intervertebral disc degeneration.

Accumulation of advanced glycation end products (AGEs) causes apoptosis in human nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IVDD). The purpose of this study was to determine the roles of thioredoxin-interacting protein (TXNIP) in the mechanisms underlying AGE-induced apoptosis of NPCs. TXNIP was silenced or overexpressed in HNPCs exposed to AGEs. Glycolysis was assessed using extracellular acidification rate (ECAR), ATP level, GLUT1, and GLUT4 measurements. AGEs, TXNIP, GLUT1, and GLUT4 levels in IVDD patients were measured as well. In NPCs, AGEs reduced cell viability, induced apoptosis, inhibited glycolysis, and increased TXNIP expression. Silencing TXNIP compromised the effects of AGEs on cell viability, apoptosis, and glycolysis in NPCs. Furthermore, TXNIP overexpression resulted in decreased cell viability, increased apoptotic cells, and glycolysis suppression. Furthermore, co-treatment with a glycolysis inhibitor improved TXNIP silencing's suppressive effects on AGE-induced cell injury in NPCs. In IVDD patients with Pfirrmann Grades II-V, increasing trends in AGEs and TXNIP were observed, while decreasing trends in GLUT1 and GLUT4. AGE levels had positive correlations with TXNIP levels. Both AGE and TXNIP levels correlated negatively with GLUT1 and GLUT4. Our study indicates that TXNIP plays a role in mediating AGE-induced cell injury through suppressing glycolysis. The accumulation of AGEs, the upregulation of TXNIP, and the downregulation of GLUT1 and GLUT4 are all linked to the progression of IVDD.