Hypoxia inhibits intervertebral disc degeneration by maintaining autophagy circadian rhythm via the HIF1α-PER2-mTOR pathway

INTRODUCTION: Disruption of the circadian rhythm (CR) and autophagy in intervertebral discs contributes to intervertebral disc degeneration (IDD) progression. However, the circadian regulation of autophagy requires further investigation. OBJECTIVES: We observed the expression of circadian proteins and autophagic markers of nucleus pulposus (NP) cells followed a diurnal rhythmic pattern in vivo and in vitro. METHODS: , followed by western blotting for CR proteins, HIF-1α, and autophagy markers. siRNA knockdown of PER2 or HIF-1α was performed to assess their roles in regulating autophagy, ECM, and CR-associated proteins. RESULTS: and autophagic stimulator could promote the rebalance of ECM metabolism. CONCLUSION: Our study demonstrates that hypoxia maintains the intrinsic CR and autophagy rhythm through the HIF-1α/PER2/mTOR pathway to prevent IDD.