Intervertebral Disc Degeneration (IVDD) is one of the most important causes of chronic low back pain,and its high prevalence and far-reaching impact on patients' quality of life have made it a major research priority in the field of public health. The mechanism of IVDD is complex and involves disturbances in cellular metabolism,an imbalance in the extracellular matrix (ECM),inflammatory response,and a combination of multiple external risk factors. In recent years,the role of circadian rhythm (CR) in IVDD has received increasing attention. Circadian rhythm regulates cellular metabolism,inflammation and apoptosis through core clock genes (e.g.,BMAL1 and CLOCK),and its disruption may accelerate the progression of IVDD. In IVDD,the disruption of circadian rhythm is manifested as a significant decrease in the expression of the genes of BMAL1 and CLOCK,which is closely associated with the elevation of inflammatory factors,the exacerbation of oxidative stress,and the apoptosis of cells. Experimental studies suggest that dysregulation of circadian core genes is one of the potential mechanisms for the pathogenesis of IVDD,and its effects may be realized through the regulation of metabolic and apoptotic pathways in myeloid cells. Pharmacologic interventions show promise in IVDD and circadian rhythm research. Drugs such as melatonin (MLT) and rapamycin (Rapa) ameliorate the pathology of IVDD by regulating the expression of circadian core genes and restoring circadian rhythm stability while alleviating inflammatory responses and oxidative stress. In summary,the pathogenesis of IVDD involves multilevel molecular and cellular mechanisms,in which circadian rhythm disruption plays a key role. In-depth study of the regulatory mechanism of circadian rhythm in IVDD not only provides new targets for early intervention and treatment of IVDD,but also opens up a new direction for the study of metabolic disorder-related diseases.
