The circadian rhythm in intervertebral disc degeneration: an autophagy connection

Abstract

There is one circadian clock in the central nervous system and another in the peripheral organs, and the latter is driven by an autoregulatory molecular clock composed of several core clock genes. The height, water content, osmotic pressure and mechanical characteristics of intervertebral discs (IVDs) have been demonstrated to exhibit a circadian rhythm (CR). Recently, a molecular clock has been shown to exist in IVDs, abolition of which can lead to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Autophagy is a fundamental cellular process in eukaryotes and is essential for individual cells or organs to respond and adapt to changing environments; it has also been demonstrated to occur in human NPCs. Increasing evidence supports the hypothesis that autophagy is associated with CR. Thus, we review the connection between CR and autophagy and the roles of these mechanisms in IDD.

Disc degeneration: Damage from disrupted cellular circadian rhythms

Disruption of molecular activities that follow a 24-hour cycle, known as a circadian rhythm, can promote the degeneration of the discs between vertebrae by affecting the natural degradation of cellular components known as autophagy. Zhang Taiwei and colleagues at Fudan University in Shanghai, China, review the role of autophagy in mediating a connection between the circadian rhythm within intervertebral disc cells and disc degeneration. Some evidence suggests that while normal autophagy maintains discs, dysfunction in the circadian rhythm within disc cells can initiate damaging excessive autophagy. The influences leading to such dysfunction include nutritional status and behavioural factors including night-shift work and otherwise disrupted sleep patterns. Contradictory evidence, however, suggests that further investigation is needed to clarify the molecular mechanisms that link circadian rhythms, autophagy and disc degeneration.