Quantification of keratan sulfate in blood as a marker of cartilage catabolism

Abstract

We have developed an enzyme-linked immunosorbent-inhibition assay which makes use of a moinoclonal antibody specific for keratan sulfate to quaintify keratan sulfate present as single chains in adult hurnan serum. In adults hospitalized with conditions not thought to affect the turnover of keratan sulfate-contairiing tissues, the serum levels varied from individual to individual (53-1,009 ng/ml) but did not show significant differences with respect to age, sex, or disease category. There were no significant differences between the serum levels of adult hospitalized patients and those of nonhospitalized normal adults. In contrast, the concentration of keratan sulfate in the sera of children aged 5-12 was significantly higher. No keratan sulfate was detected in the sera of 3 adult patients with macular corneal dystrophy, an inherited disorder of the cornea. This may indicate that individuals with macular corneal dystrophy have no keratan sulfate-containing proteoglycans in their cartilage. Adult patients with osteoarthritis have significantly higher concentrations of circulating keratan sulfate. This suggests that the assay could prove valuable in monitoring increased cartilage catabolism in joint diseases.The majority of proteoglycans (PGs) in cartilage are large molecular weight macromolecules that endow cartilage with its ability to undergo reversible deformation (1). These complex carbohydrates consist of a core protein ( M , = 25&380 x lo3) to which glycosaminoglycans (GAGS) and both 0-and N-linked oligosaccharides are covalently attached (1). In humans and many other species, there are over 100 chondroitin sulfate (CS) and keratan sulfate (KS) GAG side chains in a single PG monomer.The rate at which cartilage PGs turn over ( 2 4 ) and the mechanisms involved in the degradation of PGs in normal and pathologic cartilage (1 3-7) remain in question. There have been numerous reports of both anabolic and catabolic alterations in cartilage in diseases such as osteoarthritis (OA), rheumatoid arthritis, disc degeneration, and other diseases in which these tissues are affected (8-10). The absence of significant amounts of partially degraded PGs in normal cartilage matrix (1 1) suggests that individual PG molecules normally are rapidly degraded into smaller

Serum keratan sulfate levels in osteoarthritis patients

“…Seventy-seven percent of OA patients, but only 12% of control subjects, had KS levels which exceeded the mean + 1 SD of the control group, i.e., 312 ng KSlml. The values obtained for the control group were essentially the same as those previously found in individuals of similar age without joint disease (6).…”

“…Extracellular proteases degrade the macromolecules by fragmenting the core protein (43). These fragments diffuse out of cartilage into synovial fluid andor other body fluids, where further degradation may occur before they are eliminated from the circulation in the liver or through the kidneys (6). Unlike other carbohydrate constituents of proteoglycans, essentially all KS in the body is found in cartilage, including intervertebral discs (6,7).…”

“…Chymopapain-induced degradation of an intervertebral disc or of articular cartilage leads to a rapid rise in serum KS levels that lasts several days (8,9). Thus, serum KS determination may be used to assess proteoglycan catabolism in cartilage (6).…”

“…31, No. 5 (May 1988) to the amount of cartilage proteoglycan lost from tissues (6). The fact that serum KS levels are raised in some patients with osteoarthritis (OA) has suggested that this approach may be used to monitor the extent of cartilage degradation in affected joints (6,7).…”

“…5 (May 1988) to the amount of cartilage proteoglycan lost from tissues (6). The fact that serum KS levels are raised in some patients with osteoarthritis (OA) has suggested that this approach may be used to monitor the extent of cartilage degradation in affected joints (6,7). These preliminary findings, however, do not rule out the possibility that elevated levels may be indicative of a more generalized disorder involving cartilage in which there is no clinically apparent abnormality (7).…”