The structure and degradation of aggrecan in human intervertebral disc.
The ability of the intervertebral disc to resist compression is dependent on its high proteoglycan concentration. The disc proteoglycans are classified as aggregating or non-aggregating depending on their ability to interact with hyaluronan. The majority of the aggregating proteoglycans are derived from aggrecan, though their glycosaminoglycan substitution pattern has not been determined. In contrast, the origin of the non-aggregating proteoglycans is unclear, though it has been postulated that they are derived from aggrecan by proteolysis. The present work demonstrates that keratan sulfate (KS) in the glycosaminoglycan-binding region of disc aggrecan is confined to the KS-rich domain of the core protein and is not present in association with chondroitin sulfate (CS) in the CS1 and CS2 domains. It also shows that the non-aggregating disc proteoglycans are derived from aggrecan, with the large molecules possessing both the KS-rich and CS1 domains and the smaller molecules being generated from either the KS-rich or CS2 domain. The origin and spectrum of disc proteoglycan heterogeneity is the same in both the annulus fibrosus and nucleus pulposus.
Roughley
Peter J
PJ
Genetics Unit, Shriners Hospital for Children, Montreal, QC, Canada. proughley@shriners.mcgill.ca
Melching
Lee I
LI
Heathfield
Terrence F
TF
Pearce
Richard H
RH
Mort
John S
JS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000737:chemistry / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D002356:Cartilage / Q000737:chemistry / Q000378:metabolism*; D005333:Fetus; D006801:Humans; D007403:Intervertebral Disc / Q000737:chemistry / Q000378:metabolism*; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000503:physiopathology; D007633:Keratins / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged; D017434:Protein Structure, Tertiary / Q000502:physiology; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism
D053674:Aggrecans; D011509:Proteoglycans; D007633:Keratins