Circadian regulation in intervertebral disc degeneration: mechanisms and clinical implications.

Circadian rhythms are essential for maintaining intervertebral disc (IDD) homeostasis and regulate cellular metabolism, mechanical responses, and therapeutic efficacy. Core clock genes, especially CLOCK and BMAL1, have central roles in controlling energy metabolism, autophagy, and extracellular matrix production in disc cells. When circadian rhythms are disturbed, the progression of intervertebral disc degeneration (IDD) can be accelerated through increased inflammatory activity and impaired nutrient supply, which is particularly harmful in the avascular environment of the disc. Circadian regulation also influences how disc cells adapt to mechanical stress, thereby helping maintain disc structure and function under both normal and pathological loading conditions. As a result, people who are chronically affected by circadian disruption, such as shift workers or individuals with long-term sleep loss, may have a higher risk of developing IDD. From a therapeutic perspective, strategies based on circadian regulation, including light therapy, time-restricted feeding, and chronotherapy, have shown potential to slow or even reverse degenerative changes by re-establishing synchrony with endogenous biological rhythms. This review summarizes the role of circadian rhythms in IDD homeostasis and IDD progression, and further discusses the clinical significance of circadian-targeted approaches for the prevention and treatment of spinal disorders.