Molecular Changes in the Degenerated Goat Intervertebral Disc

In Brief 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. Summary 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. Biochemical and RNA content of goat intervertebral discs, degenerated with chondroitinase ABC, were analyzed. In the nucleus pulposus, the ratio between proteoglycans and collagens decreased whereas collagen content increased and the number of collagen cross-links decreased. Also, collagen type I and matrix metalloproteinases-13 gene expression increased, whereas aggrecan expression decreased, as observed in humans. These findings corroborate the goat disc degeneration model.