Release of cartilage macromolecules into the synovial fluid in patients with acute and prolonged phases of reactive arthritis

Abstract

Objective. Extensive changes in articular cartilage metabolism occur during the acute phase of reactive arthritis, as indicated by altered release of cartilage macromolecules into synovial fluid (SF) demonstrated immunochemically. Nevertheless, permanent cartilage lesions are rare in this disease. To monitor specific events during the evolution of reactive arthritis, we investigated the content of cartilage macromolecules in sequentially obtained SF samples from 22 patients.Methods. Two groups of proteoglycan epitopes, the glycosaminoglycan-rich region of aggrecan (referred to as proteoglycan) and its hyaluronan-binding region (HABr), as well as one matrix protein, cartilage oligo- Results. SF proteoglycan concentrations, which were initially elevated, decreased significantly with prolonged arthritis, whereas COMP levels changed less markedly and levels of HABr remained stable. There was a positive correlation between SF and serum concentrations of COMP in samples obtained during the early phase of the disease.Conclusion. Cartilage involvement in reactive arthritis is transient, in contrast to findings in rheumatoid arthritis. Reactive arthritis should therefore be a suitable model for studies of repair processes in cartilage, which will facilitate understanding of the pathophysiology of cartilage involvement in arthritis.Reactive arthritis is characterized by the acute onset of arthritis in one or a few joints following an infection, most often of the urinary or gastrointestinal tract (1). Viable organisms are not found in the joint. In the majority of cases the disease is self-limited, and radiographically visible joint damage rarely develops. Nevertheless, previous work has indicated that articular cartilage is involved in the disease process (2).Major constituents of the organic matrix of articular cartilage are type I1 collagen fibers and the cartilage-specific, large aggregating proteoglycan, aggrecan (3). The function of cartilage depends on both the highly polyanionic proteoglycan aggregates and the collagen fibers. A number of other matrix constituents have essential roles in regulating the assembly of the matrix and in participating in interactions necessary for the integrity of the tissue. One such noncol-

Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes

“…This must be taken into consideration when synovial fluid COMP levels are measured in patients with inflammatory or degenerative joint diseases and used as indicators of anabolic or catabolic events in the articular cartilage. COMP levels in serum are being utilized to monitor accelerated joint damage in patients with RA or osteoarthritis, and a positive correlation between these 2 parameters has been established in some cases (12,15,38). Since synovial cells can contribute to the pool of COMP released into the circulation, increased COMP levels may be indicative of synovitis, which could directly or indirectly contribute to joint erosion.…”

Noncollagenous, nonproteoglycan macromolecules of cartilage

“…During development, thrombospondin-3 (which binds heparin) has also been shown to be present in cartilage, as well as other tissues [34]. COMP is a useful marker for the characterization of erosive cartilage disorders, as fragments of COMP can be found in the synovial fluid of patients with erosive cartilage damage [35]. Serum levels of COMP are associated with progression of osteoarthritis [36].…”

Cartilage macromolecules in knee joint synovial fluid. Markers of the disease course in patients with acute oligoarthritis

“…The concentrations in these conditions significantly exceeded the values found in RA patients with normal knee joint radiographs and a duration of synovitis comparable with that in reactive arthritis 6. Subsequently, as the joint symptoms subsided in the patients with reactive arthritis, decreasing synovial fluid concentrations of aggrecan were found 7. In RA, the synovial fluid aggrecan concentrations are highest in patients with radiographically well preserved joints and lower values are found in stages with pronounced joint damage 6…”

“…In RA, the synovial fluid aggrecan concentrations are highest in patients with radiographically well preserved joints and lower values are found in stages with pronounced joint damage 68 In contrast, the synovial fluid content of another primarily cartilage derived macromolecule, cartilage oligomeric matrix protein (COMP), does not appear to vary considerably in different phases of reactive arthritis or RA 78 The ratio between the concentrations of these markers in synovial fluid has been used to reduce the confounding effect of variations in amounts of retrievable fluid, regardless of the fact that the clearance rates of the molecules may vary 8…”