ARRB1 inhibits extracellular matrix degradation and apoptosis of nucleus pulposus cells by promoting autophagy and attenuates intervertebral disc degeneration

Objective: Intervertebral disc degeneration (IVDD) is the leading cause of lower back pain (LBP). beta -arrestin 1 (ARRB1) is a multifunctional protein that regulates numerous pathological processes. The aim of this study was to investigate the role of ARRB1 in IVDD. Methods: The expression of ARRB1 in nucleus pulposus (NP) of rats with IVDD was assayed. Next, rat nucleus pulposus cells (NPCs) were infected with lentiviruses containing sh Arrb1 (LV-sh Arrb1 ) and overexpressing Arrb1 (LV-oe Arrb1 ). The roles of Arrb1 in serum-deprived NPCs were investigated by measuring apoptosis, extracellular matrix degradation, and autophagic flux. For experiments in vivo , LV-oe Arrb1 lentivirus was injected into the NP tissues of IVDD rats to evaluate the effects of Arrb1 overexpression on NP. Results: In the NP tissues of IVDD rats, ARRB1 and cleaved caspase-3 expression increased, and the ratio of LC3II/ LC3I protein expression was upregulated. Arrb1 knockdown aggravated extracellular matrix degradation, cellular apoptosis, and impairment of autophagic flux in rat NPCs under serum-deprived conditions, whereas Arrb1 overexpression significantly reversed these effects. ARRB1 interacted with Beclin 1, and Arrb1 knockdown suppressed the formation of the Beclin1-PIK3C3 core complex. The autophagy inhibitor 3-methyladenine (3-MA) offset the protective effects of Arrb1 overexpression in serum-deprived NPCs. Furthermore, Arrb1 overexpression inhibited apoptosis and extracellular matrix degradation, promoted autophagy in NP, and delayed the development of IVDD in rats. Conclusion: ARRB1 prevents extracellular matrix degradation and apoptosis of NPCs by upregulating autophagy and ameliorating IVDD progression, presenting an innovative strategy for the treatment of IVDD.