Ri. Inkinen et al., RELATIVE INCREASE OF BIGLYCAN AND DECORIN AND ALTERED CHONDROITIN SULFATE EPITOPES IN THE DEGENERATING HUMAN INTERVERTEBRAL DISC, Journal of rheumatology, 25(3), 1998, pp. 506-514
Objective. Proteoglycans are major components of the extracellular mat
rix of the intervertebral disc. They are vital for the biomechanical p
roperties of the tissue, and are subject to changes in disc degenerati
on. We aimed to further define these changes and their relationship to
normal aging. Methods. Normal discs (age 13-53 years, n = 6) were ana
lyzed from 5 different sites across the sagittal anterior-posterior di
rection. Degenerated anterior annulus fibrosus was collected from 7 pa
tients aged 39-46 years. Extracted proteoglycans were separated using
agarose and polyacrylamide gel electrophoresis and detected with tolui
dine blue staining and Western blotting. Results. The center of the di
sc showed the highest level of total proteoglycans, but lowest levels
of decorin and biglycan. Western blots displayed reduced signal for bo
th glycanated and nonglycanated biglycan and decorin after adolescence
, while an increased signal of biglycan was observed in degenerated an
nuli. The 7D4(-) and 3B3(-) epitopes on native chondroitin sulfate cha
ins were present in the large proteoglycans of intervertebral discs, b
ut their signal intensity had no correlation to degeneration. Chondroi
tinase ABC digestion of the blots brought up 7D4(+) signal in the smal
l proteoglycans of degenerated, but not in healthy tissue. Decrease or
total loss of 2B6(+) epitope (indicating 4-sulfated stubs of chondroi
tin sulfate chains) were found in the large proteoglycans of all degen
erated annuli. Conclusion. Human intervertebral disc degeneration invo
lves the accumulation of decorin and biglycan relative to other uronic
acid containing proteoglycans, the disappearance of 4-sulfated core r
egion in aggrecan-like large proteoglycans, and the emergence of a cor
e structure in the chains of small proteoglycans reacting with the 7D4
antibody; these findings indicate a fundamental alteration in matrix
properties that may contribute to the pathogenesis of the disease.