High levels of aggrecan aggregate components are present in synovial fluids from human knee joints with chronic injury or osteoarthrosis

Abstract

One new approach which has considerable potential for use in the diagnosis and prognosis of osteoarthrosis (OA) is the determination of biochemical markers in body fluids, and aggrecan, the major proteoglycan of articular cartilage, has been identified as a candidate marker (Israel et al. 1991, Lohmander et al. 1989, 1993. Ratcliffe et al. 1992, Saxne et al. 1985, 1986). In the matrix the aggrecan molecules form large aggregates by binding to hyaluronan, and this interaction is stabilized by a separate link protein. Catabolism of the aggrecan aggregates results in cleavage of the aggrecan protein core and link protein at specific sites, and the fragments are released from the cartilage into the synovial fluid. In normal tissue these are events of maintenance, but in degenerative cartilage proteoglycan catabolism occurs at accelerated rates. Previous studies have shown that the levels of specific components of the aggrecan aggregate, including the sulfated glycosaminoglycan (S-GAG). keratan sulfate (KS) and link protein, in synovial fluid can indicate increased catabolism in cartilage at early stages of OA (Israel el al. 1991, Ratcliffe et al. 1992. 1994). Recent studies have shown dial the monoclonal antibody 3B3 recognizes a chondroitin sulfate epitope (termed 3B3(-)) that is expressed in OA cartilage and can be detected in synovial fluid of OA joints, but is not present in normal articular cartilage and synovial fluids (Carney et al. 1992, Caterson et al. 1990, Ratcliffe et al. 1993, Slater et al. 1992, Visco et al. 1993). The objective of this study was to use the approach of Quantitative determination of specific aggrecan aggregate components in synovial fluids from patients with joint disease characterized by arthroscopy, thereby allowing an accurate comparison of the joint fluid analysis with clinical joint disease.