Time course investigation of intervertebral disc degeneration in a rat-tail puncture model

Life Sci. 2016 Jul 1:156:15-20. doi: 10.1016/j.lfs.2016.05.020. Epub 2016 May 16.

Abstract

Aims: Intervertebral disc (IVD) degeneration was believed to contribute to lower back pain. The aim of the study was to investigate the pathogenesis and regulatory mechanism of puncture-induced IVD degeneration.

Main methods: We established a rat-tail puncture model using Kirschner wire and a homemade stopper. The progress of disc degeneration was evaluated by histological examination and the quantitative measurement of type I, type II collagen and other factors expression at 0.5, 1, 2, 6, and 12weeks after puncture and was compared with control rats of the same age.

Key findings: Histological examination and Safranin-O staining revealed progressive degeneration of the punctured disc. Matrix metalloproteinase 13 (MMP13) was increased at 1week after puncture but did not change in the control group. The interleukin-1 beta (IL-1β) mRNA expression level was elevated at the acute stage after puncture compared with the control group. The hypoxia inducible factor 2 (HIF-2) increased expression in punctured groups. Additionally, compare to adjacent non-punctured segments, HIF-2α expression level transiently increased and then decreased in the nucleus pulposus immediately following puncture, and it then increased 12weeks after puncture.

Significance: The degenerative changes observed in this rat-tail puncture model are similar to human disc degeneration and that this model may be valuable for elucidating the molecular mechanisms and pathways underlying disc degeneration.

Keywords: HIF-2; Intervertebral disc degeneration; Nucleus pulposus; Rat-tail puncture model.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Collagen Type I / metabolism
  • Collagen Type II / metabolism
  • Disease Models, Animal
  • Interleukin-1beta / metabolism
  • Intervertebral Disc Degeneration / metabolism
  • Intervertebral Disc Degeneration / pathology*
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Nucleus Pulposus / metabolism
  • Nucleus Pulposus / pathology
  • Punctures*
  • Rats, Sprague-Dawley
  • Tail
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Collagen Type I
  • Collagen Type II
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • endothelial PAS domain-containing protein 1
  • Matrix Metalloproteinase 13