Targeting the IL-1β/IL-1Ra pathways for the aggregation of human islet amyloid polypeptide in an ex vivo organ culture system of the intervertebral disc

Exp Mol Med. 2019 Sep 25;51(9):1-16. doi: 10.1038/s12276-019-0310-7.

Abstract

Intervertebral disc degeneration (IDD) is characterized by excessive apoptosis of nucleus pulposus (NP) cells and hyperactive extracellular matrix (ECM) catabolism. Our previous studies revealed the relationship between human islet amyloid polypeptide (hIAPP) and NP cell apoptosis. However, the role of hIAPP aggregates in IDD has not yet been investigated. This study aimed to determine whether the accumulation of hIAPP aggregates promotes IDD progression. The aggregation of hIAPP increased in human NP tissues during IDD. The deposition of hIAPP aggravated the compression-induced IDD that promoted NP cell apoptosis and ECM degradation via IL-1β/IL-1Ra signaling in an ex vivo rat disc model. Moreover, neutralizing IL-1β augmented the protective effects of hIAPP overexpression by decreasing hIAPP aggregation in human NP cells. These results suggest that the aggregation of hIAPP promotes NP cell apoptosis and ECM degradation ex vivo and in vitro by disrupting the balance of IL-1β/IL-1Ra signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Disease Models, Animal
  • Extracellular Matrix / genetics
  • Gene Expression Regulation / genetics
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Interleukin-1beta / genetics*
  • Intervertebral Disc Degeneration / genetics*
  • Intervertebral Disc Degeneration / pathology
  • Islet Amyloid Polypeptide / genetics*
  • Nucleus Pulposus / metabolism
  • Protein Aggregation, Pathological
  • Rats
  • Signal Transduction / genetics

Substances

  • IL1B protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Islet Amyloid Polypeptide