Accelerated intervertebral disc degeneration in scoliosis versus physiological ageing develops against a background of enhanced anabolic gene expression.
Molecular consequences of long-term deformation and altered mechanical loading of intervertebral disc (IVD) tissue in scoliosis have yet to be elucidated. We hypothesized that histological disc degeneration is faster in scoliosis than in normal ageing and that this is reflected by an altered gene expression profile. A semiquantitative histodegeneration score (HDS) revealed significantly enhanced degeneration in scoliosis (HDS 5.3) versus age-matched control IVDs (HDS 2.25; p = 0.001). Gene expression analysis by cDNA array and RT-PCR demonstrated higher mRNA levels for extracellular-matrix molecules like aggrecan, biglycan, decorin, lumican, chondromodulin, and COL2A1 in scoliotic discs versus normal discs of identical degeneration score. No differences were evident for catabolic molecules like MMP3, MMP13, MMP17, and TIMP1. In sum, morphologic disc degeneration was accelerated by about 2 decades in scoliosis versus physiological ageing and developed against a background of stronger anabolic matrix metabolism at younger age or in response to the altered mechanical environment of the tissue.
Bertram
Helge
H
Division of Experimental Orthopaedics, Orthopaedic University Hospital Heidelberg, D-69118 Heidelberg, Germany.
Steck
Eric
E
Zimmerman
Gerald
G
Chen
Bohua
B
Carstens
Claus
C
Nerlich
Andreas
A
Richter
Wiltrud
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology*; D016022:Case-Control Studies; D002648:Child; D017364:Collagenases / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D008297:Male; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012600:Scoliosis / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; C507079:MMP13 protein, human; C402225:MMP17 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated