Effects of kartogenin on the attenuated nucleus pulposus cell degeneration of intervertebral discs induced by interleukin-1β and tumor necrosis factor-α

Int J Mol Med. 2018 Feb;41(2):749-756. doi: 10.3892/ijmm.2017.3283. Epub 2017 Nov 24.

Abstract

Cytokines are the main cause of intervertebral disc degeneration. Kartogenin (KGN) is found to protect chondrocytes from cytokines. To explore whether KGN can slow down the degeneration on intervertebral discs following exposure to interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF‑α), the expression of type II collagen (Col II) and aggrecan were detected by immunofluorescence, immunohistochemistry and tissue staining. An in vitro model of disc degeneration using human nucleus pulposus cells (hNPCs) and ex vivo culture of mouse intervertebral discs organs under the actions of inflammatory cytokines were used, and the expression of Col II and aggrecan in hNPCs were detected by semi-quantitative western blot analysis, and the mRNA expression of the genes than encode Col II and aggrecan were detected by reverse transcription‑quantitative polymerase chain reaction (RT-qPCR). The results indicated that the expression of Col II and aggrecan was reduced in the degeneration models. However, the protein expressions of Col II and aggrecan were significantly elevated in hNPCs and the mouse intervertebral discs following addition of KGN. RT-qPCR results revealed that the mRNA expression of Col II and aggrecan was increased in hNPCs and mouse intervertebral discs following treatment with KGN. Thus, KGN effectively increased the expression of Col II and aggrecan in hNPCs and slowed the degeneration of intervertebral discs stimulated by IL-1β and TNF-α.

MeSH terms

  • Aggrecans / genetics*
  • Anilides / administration & dosage*
  • Animals
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Collagen Type II / genetics*
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-1beta / administration & dosage
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / metabolism
  • Intervertebral Disc / pathology
  • Intervertebral Disc Degeneration / drug therapy*
  • Intervertebral Disc Degeneration / pathology
  • Mice
  • Nucleus Pulposus / cytology
  • Nucleus Pulposus / drug effects
  • Phthalic Acids / administration & dosage*
  • Tumor Necrosis Factor-alpha / administration & dosage

Substances

  • Aggrecans
  • Anilides
  • Collagen Type II
  • Interleukin-1beta
  • Phthalic Acids
  • Tumor Necrosis Factor-alpha
  • kartogenin