Excessive cholesterol accelerates intervertebral disc degeneration by promoting the polarization of M1 macrophages.

Background: Intervertebral disc degeneration (IVDD) is the primary cause of low back pain (LBP). Dyslipidaemia can induce a chronic inflammatory state in the body, promote the polarization of macrophages, and may affect the homeostasis of the intervertebral disc (IVD). However, the relationship between dyslipidaemia and IVDD remains unclear.

Methods: This study encompassed human subjects and animal models. Techniques used: cell counting kit-8 (CCK8), western blotting, immunofluorescence staining, immunohistochemical staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and statistical analysis.

Results: Through a retrospective analysis involving 196 patients, this study found that high TC, TG, and LDL-C levels were risk factors for IVDD. Subsequently, cell experiments and animal models verified that excessive cholesterol can directly induce the loss of phenotype in nucleus pulposus cells and promote the M1-type polarization of macrophages through the JAK1/STAT1 pathway, thereby accelerating IVDD.

Conclusions: These results reveal that excessive cholesterol is a risk factor for intervertebral disc degeneration, emphasizing its direct role in the degeneration process as well as its involvement in signal regulation during macrophage polarization. Therefore, cholesterol-lowering therapy may provide new opportunities for the treatment of IVDD.