Stimulation of gene expression and loss of anular architecture caused by experimental disc degeneration--an in vivo animal study

Spine (Phila Pa 1976). 2005 Nov 15;30(22):2510-5. doi: 10.1097/01.brs.0000186591.17114.e9.

Abstract

Study design: An external compression model was used to evaluate gene and protein expression in intervertebral discs with moderate disc degeneration.

Objective: To determine messenger ribonucleic acid and protein expression levels of relevant disc components.

Summary of background data: An animal model of mechanically induced disc degeneration was developed and characterized histologically. However, little is known at the molecular level in moderate disc degeneration.

Methods: There were 8 New Zealand white rabbits subjected to monosegmental posterior compression to induce moderate disc degeneration. Twelve animals served as controls or sham controls. Discs were analyzed using immunohistochemistry for collagen type 1 (COL1), COL2, aggrecan, and bone morphogenetic protein-2/4 (BMP-2/4). For gene analysis, conventional and quantitative polymerase chain reactions were used for COL1A2, COL2A1, aggrecan, BMP-2, biglycan, decorin, osteonectin, fibromodulin, fibronectin, matrix metalloproteinase-13 (MMP-13), and tissue inhibitor of MMP-1. Gene expression for nontreated, sham-treated, and compressed discs was quantified in relation to the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase.

Results: Immunohistochemistry of compressed discs showed a loss of anular architecture, and a significant reduction of BMP-2/4 and COL2 positive cells. Gene expression analysis showed a significant up-regulation of COL1A2, osteonectin, decorin, fibronectin, tissue inhibitor of MMP-1, BMP-2, and MMP-13 in compressed discs.

Conclusions: Experimental moderate disc degeneration is characterized by a loss of BMP-2/4 and COL2 positive cells, although gene expression of disc constituents, catabolic enzymes, and growth factors is stimulated to reestablish disc integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans
  • Animals
  • Biglycan
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Collagen / genetics
  • Collagen / metabolism
  • Collagenases / genetics
  • Collagenases / metabolism
  • Decorin
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Fibromodulin
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression / physiology*
  • Immunohistochemistry
  • Intervertebral Disc / physiology*
  • Intervertebral Disc Displacement / genetics*
  • Intervertebral Disc Displacement / physiopathology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 13
  • Osteonectin / genetics
  • Osteonectin / metabolism
  • Proteoglycans / genetics
  • Proteoglycans / metabolism
  • Rabbits

Substances

  • Aggrecans
  • Biglycan
  • Bone Morphogenetic Proteins
  • Decorin
  • Extracellular Matrix Proteins
  • Fibronectins
  • Lectins, C-Type
  • Osteonectin
  • Proteoglycans
  • Fibromodulin
  • Collagen
  • Collagenases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 1