Title
Molecular changes in the degenerated goat intervertebral disc
Author
Hoogendoorn, R.
Doulabi, B.Z.
Huang, C.L.
Wuisman, P.I.
Bank, R.A.
Helder, M.N.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
Study Design. Caprine lumbar intervertebral discs (IVD) were collected from previous studies and categorized as normal, mildly, or severely degenerated. The biochemical composition and the RNA profiles present in both the nucleus pulposus (NP) and the anulus fibrosus (AF) were analyzed. Objective. To determine the molecular changes occurring in a disc degeneration model, evaluating the mechanism through which the degeneration develops in this model. Summart of Background Data. Recently we described an IVD degeneration model in the goat by injecting chondroitinase ABC. This results in mild progressive disc degeneration. Methods. One hundred nine caprine IVDs were assigned to 3 classes: no degeneration, mild, or severe degeneration. Collagen content, collagen cross-links (hydroxylysyl pyridinoline) and the ratio between the glycosaminoglycans (GAGs) and hydroxyprolines (Hyp) (GAG/Hyp ratio) in the NP and AF samples were studied. Furthermore, the gene expression of collagen type I, type II, and aggrecan as well as a desintegrin and metalloproteinase with thrombospondin motifs (ADAMTIS)-2, ADAMTS-14, and matrix metalloproteinases-13 were studied. Results. Collagen content was increased in severely degenerated NPs and decreased in severely degenerated AFs. Collagen cross-links were decreased in the severely degenerated NPs indicating de novo deposition of immature, reducible cross-linked collagens. The GAG/Hyp ratio found in none-degenerate goat discs was comparable to human ratios and decreased in degenerated discs, similar as in humans. The ADAMTS genes were increasingly detectable in the degenerated discs. The matrix metalloproteinases-13 gene increased significantly in degenerated discs. The expression of collagen type I increased in degenerated discs while aggrecan decreased. Conclusion. Changes in the GAG/Hyp ratio of chemically induced degeneration in goat IVD resemble the changes seen in humans. Gene expression profiles match the pattern of degeneration, suggesting that the injection of chondroitinase ABC might mimic the onset of human disc degeneration. © 2008 Lippincott Williams & Wilkins.
Subject
Biomedical Research
Animal model
Biochemical composition
Disc degeneration
Gene expression
aggrecan
chondroitin ABC lyase
collagen
collagen type 1
collagen type 2
collagenase 3
glycosaminoglycan
hydroxyproline
metalloproteinase
pyridinoline
thrombospondin
scleroprotein
animal experiment
animal model
article
cross linking
disease severity
female
gene expression
gene sequence
goat
intervertebral disk
intervertebral disk degeneration
nonhuman
priority journal
protein motif
animal
comparative study
disease model
gene expression profiling
genetics
lumbar vertebra
metabolism
methodology
pathology
physiology
spine disease
Animals
Collagen
Disease Models, Animal
Extracellular Matrix Proteins
Female
Gene Expression Profiling
Goats
Intervertebral Disk
Lumbar Vertebrae
Spinal Diseases
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http://resolver.tudelft.nl/uuid:8af7e41d-e940-4b44-befc-a7d6058618c8
DOI
https://doi.org/10.1097/brs.0b013e31817d2468
TNO identifier
240914
ISSN
0362-2436
Source
Spine, 33 (16), 1714-1721
Document type
article