Glycosaminoglycan sulfation in human osteoarthritis. Disease-related alterations at the non-reducing termini of chondroitin and dermatan sulfate.
Chondroitin lyase products of aggrecan and small proteoglycans from normal and osteoarthritic cartilages were analyzed for chain internal Deltadisaccharides and terminal mono- or disaccharides. Chondroitin and dermatan sulfate chains from arthritic cartilages were of essentially normal size and internal sulfation but had significantly altered sulfation of the terminal residues. Whereas in normal cartilage, approximately 60% of terminal GalNAc4S was 4, 6-disulfated, it was reduced to approximately 30% in osteoarthritic cartilage. This is most likely due to a lower terminal GalNAc4, 6S-disulfotransferase activity and reveals that metabolic changes in osteoarthritis can affect this distinct sulfation step during chondroitin and dermatan sulfate synthesis. GlcAbeta1,3GalNAc6S-, the mimotope for antibody 3B3(-), was present on approximately 8 and approximately 10% of chains from normal and osteoarthritic cartilages, respectively. 3B3(-) assayed by immunodot blot was within the normal range for most osteoarthritic samples, with only 5 of 24 displaying elevated reactivity. This resulted not from a higher content of mimotope, but possibly from other structural changes in the proteoglycan that increase mimotope reactivity. In summary, chemical determination of sulfation isomers at the non-reducing termini of chondroitin and dermatan sulfate provides a reliable assay for monitoring proteoglycan metabolism not only during normal growth of cartilage but also during remodeling of cartilage in osteoarthritis.
Plaas
A H
AH
Shriners Hospital for Children, Tampa Unit, Tampa, Florida 33612, USA. annaplaas@delphi.com
West
L A
LA
Wong-Palms
S
S
Nelson
F R
FR
D000328:Adult; D002358:Cartilage, Articular / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D003871:Dermatan Sulfate / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D007719:Knee Joint; D010003:Osteoarthritis / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D006025:Glycosaminoglycans; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates