Abstract

The measurement of body fluid levels of biochemical markers in joint tissues has begun to provide clinically useful information. Synovial fluid (SF) plays an important role in articular joint lubrication, nutrition, and metabolism of cartilage and other connective tissues within the joint. The purpose of our study was to identify and characterize osteogenic protein 1 (OP-1) in SF from patients with rheumatoid arthritis (RA) or with osteoarthritis (OA) and to correlate levels of OP-1 with those of hyaluronan (HA) and antigenic keratan sulfate (AgKS). SF was aspirated from the knees of patients with either RA or OA and from the knees of asymptomatic organ donors with no documented history of joint disease. The presence of detectable OP-1 in SF was demonstrated by western blots with specific anti-pro-OP-1 and anti-mature OP-1 antibodies. Measurement of levels of OP-1, HA and AgKS was performed using ELISAs. OP-1 was identified in human SF in two forms, pro-OP-1 and active (mature) OP-1 – mature OP-1 being detected only in SF from OA patients and RA patients. Levels of OP-1 and HA were higher in RA patients than in OA patients and asymptomatic donors, while the level of AgKS was highest in SF from asymptomatic donors. Statistically significant differences were found between SF levels of OP-1 in RA and OA patients and between SF levels of AgKS among the three groups tested. The SF content of OP-1 tended to correlate positively with HA levels, but negatively with AgKS concentrations. In conclusion, the results of this study suggest that measurement of OP-1 in joint fluid may have value in the clinical evaluation of joint disease processes.

Highlights

  • Direct markers originate from cartilage structures and provide a measure of the responses of chondrocytes or changes that occur in cartilage

  • The results of this study suggest that measurement of osteogenic protein 1 (OP-1) in joint fluid may have value in the clinical evaluation of joint disease processes

  • antigenic keratan sulfate (AgKS) is released when aggrecan is cleaved by proteolytic enzymes, whereupon the AgKS-bearing fragments may be measured in various body fluids

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Summary

Introduction

Direct markers originate from cartilage structures and provide a measure of the responses of chondrocytes or changes that occur in cartilage. Among these is antigenic keratan sulfate (AgKS), a molecule found almost exclusively in aggrecan molecules within cartilaginous tissues [2,3]. The indirect markers of cartilage metabolism, on the other hand, are found in many tissues and are produced by a variety of cell types [1]. Cartilage-derived molecules present in SF may be markers predominantly of biosynthetic changes or of degradative changes Such markers of cartilage metabolism have been divided into two classes, direct markers and indirect markers [1]

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