SYNOVIAL FLUID MARKERS IN OSTEOARTHRITIS
Section snippets
MARKER MOLECULES IDENTIFIED IN A SYNOVIAL FLUID
Keratan sulfate4, 13, 14 and chondroitin sulfate4, 75, 88 are glycosaminoglycan (GAG) constituents of articular cartilage proteoglycans (PGs) that can be detected in OA synovial fluid as fragments of the aggrecan molecule (Table 1).21, 22, 35, 80, 81, 98 The synovial fluid concentration of these molecules and of type II collagen propeptide, 49, 70, 87 link protein, 74 bone sialoprotein and osteocalcin, 82, 84 cartilage oligomeric protein (COMP), 28, 48, 62 and of a cartilage matrix glycoprotein
IS MARKER CONCENTRATION MEANINGFUL?
It has been suggested that the validity of a surrogate marker that is present in the OA joint and can be linked to the pathogenesis of the disease depends, in part, on the strength of the relationship between the synovial fluid concentration of the marker and the severity of articular pathology or other indicators of clinically relevant disease.46 Unfortunately, interpretation of changes in the synovial fluid concentration of a marker molecule is highly problematic.45, 89 To understand the
REMOVAL OF SYNOVIAL FLUID MARKERS FROM THE JOINT
The turnover of proteins in synovial fluid is influenced by a number of factors that must be taken into account if the synovial fluid concentration of an articular cartilage-derived protein is to be related to the rate of its release from the articular cartilage matrix.39, 40, 41, 45 Careful experimental and theoretical work by Levick et al41 shows that trans-synovial fluid absorption obeys Starling's principles of fluid exchange, and that the integrity of the capillary wall, the composition of
SYNOVIAL FLUID MARKERS IN EXPERIMENTAL OSTEOARTHRITIS
Several studies have examined changes in the concentration of marker molecules in the canine anterior cruciate ligament transection (ACLT) model of OA.* A significant, sustained increase in the serum concentration of KS was documented in cruciate ligament-deficient dogs with early OA, 73 although other investigations have failed to confirm a significant correlation between serum KS levels and articular cartilage changes of OA in this model.7
LONGITUDINAL STUDIES OF SYNOVIAL FLUID MARKERS OF OSTEOARTHRITIS
In contrast to the many cross-sectional studies of synovial fluid markers in OA, few serial measurements of these markers are available. In healthy athletes, whose baseline synovial fluid concentration of aggrecan, stromelysin-1, TIMP-1 and procollagen II peptide were lower than those in a comparison group of patients with knee pain, vigorous exercise regimens failed to yield a statistically significant change in the concentration of any of these markers.76 Since the magnitude of changes in
CONCLUSION
Better understanding of the mechanisms responsible for breakdown and repair of articular cartilage has led to great interest in the potential utility of cartilage-derived molecules as markers of cartilage metabolism and the activity or severity of disease processes in OA.2, 53, 59, 65, 92 A daunting number of matrix proteins, enzymes, cytokines, and other macromolecules are detectable in OA synovial fluid, and specific criteria have been proposed for critical evaluation of the content,
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Address reprint requests to Stephen L. Myers, MD, Rheumatology Division, Indiana University School of Medicine, 541 Clinical Drive, Room 379, Indianapolis, IN 46202
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Rheumatology Division, Indiana University School of Medicine, Indianapolis, Indiana