Affiliation:
1. The Eighth Affiliated Hospital of Sun Yat-sen University
2. Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Abstract
Abstract
Intervertebral disc degeneration (IDD) is closely correlated with Low back pain. Apoptosis and extracellular matrix (ECM) degradation caused by inflammation-mediated NF-ĸB has been reported to promote IDD. Low-density lipoprotein receptor-related protein-1 (LRP1) was confirmed to negatively regulate NF-ĸB in many disease. Moreover, emodin has been shown to upregulate LRP1. However, the effect of emodin on IDD, more importantly, the effect of in vivo therapy and mechanism are not clear. This study aimed to investigate the effect of emodin and its target on IDD in vivo and in vitro. Alcian blue staining showed emodin effectively rescued IL-1β-induced ECM secretion. Moreover, the results of western blot showed emodin promoted matrix synthesis, inhibited matrix degradation and apoptosis in NPCs under stimulation of IL-1β. Further study showed emodin inhibited IL-1β-induced NF-ĸB. In our study, we found emodin increased protein level of LRP1 levels by inhibiting its degradation via the proteasome pathway. In addition, LRP1 knockdown blocked emodin's effects on inhibition of NF-ĸB, and thus promoted apoptosis and matrix metabolism disorder in NPCs. Emodin effectively alleviated IDD in rat model and siRNA LRP1 injection also reversed beneficial effect of emodin on IDD in rat model. In conclusion, this study showed that emodin has therapeutic effect on IDD by inhibiting matrix metabolism disorder and apoptosis through LRP1 in vitro and in vivo, which was related to LRP1-mediated inhibition of NF-ĸB. This study provided evidence for emodin as a potential drug for the treatment of IDD.
Publisher
Research Square Platform LLC
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