Characterization of intervertebral disc aging: longitudinal analysis of a rabbit model by magnetic resonance imaging, histology, and gene expression.
METHODS
A cohort of young, healthy New Zealand White rabbits was followed longitudinally with serial magnetic resonance imaging (MRI) analysis and terminal analysis of histologic changes and gene expression.


OBJECTIVE
To examine the changes observed during normal aging in the intervertebral disc.


BACKGROUND
Although there is a correlation between aging and the onset of intervertebral disc degeneration (IDD), evidence suggests that distinct pathways are involved in these processes. Our group has characterized a reproducible rabbit model of IDD by MRI, radiograph, histology, and mRNA expression. However, no similar analysis has been performed longitudinally for intervertebral disc aging to allow comparison of these 2 important processes.


METHODS
Four skeletally mature female NZW rabbits were housed for 122 weeks, and lumbar spine MRIs were characterized serially. Histologic and quantitative gene expression analysis of the nucleus pulposus of these aging animals was performed, and compared with adult and young rabbits.


RESULTS
Mean MRI index decreased by <25% through 120 weeks. The histologic analysis showed changes in cell composition, with abundant notochordal cells in the young, chondrocyte-like cells and notochordal cells in the adult, and clusters of hypertrophic chondrocytes in the aging discs. The PCR analysis of the nucleus pulposus showed that gene expression of collagen decreased, whereas that for proteoglycans increased with aging. BMP-2, TIMP-1, and SOX-9 expression was significantly lower in the young compared with adult discs and TGF-beta1 demonstrated lower gene expression in young and aging animals.


CONCLUSIONS
Although dramatic cellular changes were observed, age-related MRI changes occurred in this rabbit model of normal aging at a much slower rate than in a previous injury model of degeneration. In addition, the gene expression analysis of the nucleus pulposus demonstrated remarkable differences between aging and injury induced degeneration. These results suggest that aging and injury contribute uniquely to the process of IDD.
Sowa
Gwendolyn
G
Departments of Orthopaedic Surgery and daggerPhysical Medicine and Rehabilitation, Ferguson Laboratory for Orthopaedic Research, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Vadalà
Gianluca
G
Studer
Rebecca
R
Kompel
John
J
Iucu
Christina
C
Georgescu
Helga
H
Gilbertson
Lars
L
Kang
James
J
D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007403:Intervertebral Disc / Q000473:pathology* / Q000502:physiology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D023421:Models, Animal; D011817:Rabbits; D013122:Spinal Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology