Abstract
The depletion of chondroitin sulfates (CSs) within the intervertebral disc (IVD) during degenerative disc disease (DDD) results in a decrease in tissue hydration, a loss of fluid movement, cell apoptosis, a loss of nerve growth inhibition and ultimately, the loss of disc function. To date, little is known with regards to the structure and content of chondroitin sulfates (CSs) during IVD ageing. The behavior of glycosaminoglycans (GAGs), specifically CSs, as well as xylosyltransferase I (XT-I) and glucuronyltransferase I (GT-I), two key enzymes involved in CS synthesis as a primer of glycosaminoglycan (GAG) chain elongation and GAG synthesis in the nucleus pulposus (NP), respectively, were evaluated in a bovine ageing IVD model. Here, we showed significant changes in the composition of GAGs during the disc ageing process (6-month-old, 2-year-old and 8-year-old IVDs representing the immature to mature skeleton). The CS quantity and composition of annulus fibrosus (AF) and NP were determined. The expression of both XT-I and GT-I was detected using immunohistochemistry. A significant decrease in GAGs was observed during the ageing process. CSs are affected at both the structural and quantitative levels with important changes in sulfation observed upon maturity, which correlated with a decrease in the expression of both XT-I and GT-I. A progressive switch of the sulfation profile was noted in both NP and AF tissues from 6 months to 8 years. These changes give an appreciation of the potential impact of CSs on the disc biology and the development of therapeutic approaches for disc regeneration and repair.
Highlights
Neck and lower back pain are the two greatest causes of jobrelated disability with significant associated social and economic costs,[1] accounting for total annual healthcare costs estimated at £11 billion in the UK in 2000(ref. 2) and between $50 to $90 billion each year in the USA.[3]
The behavior of glycosaminoglycans (GAGs), chondroitin sulfates (CSs), as well as xylosyltransferase I (XT-I) and glucuronyltransferase I (GT-I), two key enzymes involved in CS synthesis as a primer of glycosaminoglycan (GAG) chain elongation and GAG synthesis in the nucleus pulposus (NP), respectively, were evaluated in a bovine ageing intervertebral disc (IVD) model
CSs are affected at both the structural and quantitative levels with important changes in sulfation observed upon maturity, which correlated with a decrease in the expression of both XT-I and GT-I
Summary
Neck and lower back pain are the two greatest causes of jobrelated disability with significant associated social and economic costs,[1] accounting for total annual healthcare costs estimated at £11 billion in the UK in 2000(ref. 2) and between $50 to $90 billion each year in the USA.[3]. The 8-year-old IVD tissues presented an increase in cellularity with induced by transforming growth factor beta 1 (TGF-β1) via characteristic clusters of multiple chondrocyte-like cells (Figure 4 extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways.[38] A decrease (1) (c), arrows). These clusters were delimited by a rim of matrix with a higher staining intensity. For this tissue, the variations in the percentages of disaccharides between the different age-groups were not significantly different (Figure 7b)
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