The Glycosaminoglycans of Normal and Arthritic Cartilage

Abstract

A B S T R A C T The cartilages from the hip joints of 13 normal and 15 osteoarthritic humans were analyzed for glycosaminoglycan content and distribution. The GAGs were separated by elution with CPC on a short cellulose column by the technique of Svejcar and Robertson after digestion of the tissue with pronase and papain.The eluates were identified by a variety of methods including determination of molar ratios, N-acetyl-hexosamine determinations after hyaluronidase treatment and thin-layer chromatography of unhydrolyzed and hydrolyzed GAGs.From the data obtained, it was demonstrated that cartilage from arthritic patients showed a significant increase in the concentration of chondroitin 4-sulfate and a significant decrease in keratan sulfate, with only slight changes in the total amount of GAG present. Calculations of the molar ratios showed variation in the sulfation -with chondroitin 4-sulfate appearing in the "supersulfated" state in the arthritic cartilage.The data lead to speculation regarding the process of osteoarthritis, and it is concluded that the changes seen are more likely to represent an altered pattern of synthesis rather than selective degradation. Since the changes suggest a younger cartilage, a theory is advanced that the chondrocyte responds to the chronic stress of osteoarthritis by modulation to a chondroblastic phase.

Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage

“…A report from our laboratory in 1971 detailed experimental evidence which suggested an altered glycosaminoglycan pattern in osteoarthritis in which the percentage of chondroitin 4-sulfate was markedly increased and that of keratan sulfate diminished (15). These findings were in part a confirmation of those by Bollet and Nance (3) and Benmaman and coworkers (32); subsequent studies by Lust and Pronsky (33), Bjelle and coworkers (34), McDevitt et a1 (7), Mankin and Lippiello ( 1 3 , and Brocklehurst and Maroudas (35) have reported a similar alteration.…”

Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.

“…In OA, where there is relatively little synovial inflammation, the cartilage matrix degradation is usually accompanied by enhanced synthesis of proteoglycans. This has been demonstrated in both the human disease (1,2) and in experimental models (3,4). In contrast, intra-articular inflammation is a major feature of RA, resulting in polymorphonuclear (PMN)-rich cellular exudates in the joints.…”

“…Destruction and remodeling of articular cartilage are features of both rheumatoid arthritis (RA) ' and osteoarthritis (OA) ( 1 ). In OA, where there is relatively little synovial inflammation, the cartilage matrix degradation is usually accompanied by enhanced synthesis of proteoglycans.…”

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

“…A potential limitation is that GAGs can be elevated due to other conditions unrelated to MPS giving false positives [e.g. : Mucolipidosis (Tomatsu et al, 2005); diabetes (Komosinska-Vassev et al, 2005); arthritis (Mankin et al, 1971); cancer (Hennessey et al, 1981)], as seen in the general NBS samples in this study. However, MPS I and II cause an elevation in three GAGs and MPS III causes an elevation in two GAGs, reducing the number of false positives.…”