The Relationship between High-Level Uric Acid and Intervertebral Disk Degeneration

Abstract

Objective: To explore the potential relationship between hyperuricemia (HUA) and intervertebral disk degeneration (IDD). Background: Lumbar disk herniation (LDH) has become an increasingly common disease in the modern era. Most studies suggest that intervertebral disc (IVD) degeneration (IDD) becomes the main cause factor of LDH. At present, the cause of HUA involving the IDD is not clear. Methods: The effect of uric acid at different concentrations (0, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 and 1200 μM) on the proliferation of human nucleus pulposus (NP) cells in culture was assessed by a Cell Counting Kit-8 (CCK-8) assay. The TdT-mediated dUTP nick end labeling (TUNEL) method was used to count apoptotic cells, and autophagy marker proteins were quantified to examine the impact of high-level uric acid at various concentrations (0, 100, 200, 400 μM) on NP cell autophagy. High levels of uric acid were studied for their potential impact on people who suffer from LDH. Results: Human NP cell viability was decreased, affected by an increase in uric acid concentration. TUNEL-positive cells in the NP cells were found to be significantly upregulated as a function of 400 μM uric acid (UA) concentration group (p < 0.01). Treatment with uric acid significantly suppressed type II collagen (COL2) messenger RNA (mRNA) expression (p < 0.001). The longer the incubation period, the less expression was seen. Both the microtubule-associated protein1 light chain3 (LC3)-II/LC3-I ratio, the Beclin1 and cleaved caspase-3 protein levels were significantly higher in uric acid-treated groups compared to the control group (p < 0.05), while the p62 protein levels were significantly lower in uric acid-treated groups compared to the control group (p < 0.001). The high levels of uric acid activated autophagy in the NP cells. Patients with LDH and HUA had significantly lower levels of COL2, aggrecan mRNA, and protein in their IVD tissues compared with those with normal uric acid levels (p < 0.05). Conclusions: High uric acid levels may reduce the extracellular matrix exression by lowering COL2, aggrecan mRNA, and protein levels, and may also activate autophagy in NP cells by increasing the levels of autophagy-related proteins. IVD tissue samples from IDD patients revealed significantly lower levels of COL2 and aggrecan in those with HUA compared to those without HUA.