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


BACKGROUND
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.
Guehring
Thorsten
T
Department of Orthopedic Surgery, University of Heidelberg, Heidelberg, Switzerland. tguehrin@ix.urz.uni-heidelberg.de
Omlor
Georg W
GW
Lorenz
Helga
H
Bertram
Helge
H
Steck
Eric
E
Richter
Wiltrud
W
Carstens
Claus
C
Kroeber
Markus
M
D053674:Aggrecans; D000818:Animals; D058578:Biglycan; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D000071235:Fibromodulin; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000502:physiology*; D007405:Intervertebral Disc Displacement / Q000235:genetics* / Q000503:physiopathology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D011817:Rabbits
D053674:Aggrecans; D058578:Biglycan; D019485:Bone Morphogenetic Proteins; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D037181:Lectins, C-Type; D015676:Osteonectin; D011509:Proteoglycans; D000071235:Fibromodulin; D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1