Morin attenuates pyroptosis of nucleus pulposus cells and ameliorates intervertebral disc degeneration via inhibition of the TXNIP/NLRP3/Caspase-1/IL-1β signaling pathway

Biochem Biophys Res Commun. 2021 Jun 25:559:106-112. doi: 10.1016/j.bbrc.2021.04.090. Epub 2021 Apr 30.

Abstract

Intervertebral disc degeneration (IDD) is a major cause of lower back pain (LBP), a condition that causes a heavy economic burden globally. The production of cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF) α, is increased in the degenerating intervertebral disc. Thioredoxin-interacting protein (TXNIP) participates in NLRP3 inflammasome-dependent pyroptosis in liver. Therefore, we hypothesized that TXNIP maypromote pyroptosis via NLRP3/Caspase-1/IL-1β signaling pathway in nucleus pulposus (NP) cell. This study examined the effects of TXNIP on IDD, explored the underlying mechanisms of action and find Morin which is the inhibitor of TXNIP can attenuates pyroptosis of nucleus pulposus cells and ameliorates intervertebral disc degeneration. Our findings indicate that TXNIP promote pyroptosis via NLRP3/Caspase-1/IL-1β signaling pathway in NP cell. Morin considerably inhibited the TXNIP/NLRP3/Caspase-1 signaling pathway in vitro. In vivo. Our data show that TXNIP can aggravates intervertebral disc degeneration and morin may be a useful therapeutic agent for IDD.

Keywords: Intervertebral disc degeneration; Morin; Pyroptosis; TXNIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Interleukin-1beta / metabolism
  • Intervertebral Disc Degeneration / drug therapy*
  • Intervertebral Disc Degeneration / metabolism
  • Intervertebral Disc Degeneration / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Nucleus Pulposus / drug effects*
  • Nucleus Pulposus / metabolism
  • Nucleus Pulposus / pathology
  • Pyroptosis / drug effects*
  • Rats
  • Signal Transduction / drug effects*

Substances

  • Cell Cycle Proteins
  • Flavonoids
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • TXNIP protein, rat
  • morin
  • Caspase 1