Effects of synovial fluid hyaluronan concentration and molecular size on clearance of protein from the canine knee.

Abstract

The synovial fluid (SF) concentration of proteins (or fragments thereof) derived from the articular cartilage may reflect the processes of cartilage breakdown or repair within an arthritic joint and, hence, serve as a marker of these processes. Because changes in the clearance kinetics of marker molecules in SF would invalidate the assumption that their concentration in SF is directly proportional to turnover of the cartilage matrix, we investigated whether reduction in the concentration and/or molecular size of hyaluronan (HA) in joint effusions affects clearance of albumin from the canine knee. The volume of distribution and clearance kinetics of radioiodinated serum albumin (RISA) were determined in normal dogs after injection of the knee with HA preparations whose concentration (3.0-0.03 mg/ml) and average molecular weight (0.2-6.1 x 10(6) Da) resembled those seen in synovial effusions, and which increased by roughly 270% the volume of fluid in the joint space. In knees injected with a physiologic concentration (3.0 mg/ml) of high molecular weight HA, the RISA distribution volume (2.8 ml) and clearance rate (1.7 microliters/min) slightly exceeded those in knees in which the SF HA concentration was reduced 55-62% by injection of 0.3-0.03 mg/ml HA, but not those in knees in which the average molecular weight of the SF HA was reduced 84% by injection of exogenous HA with a molecular weight of 2.4 x 10(5) Da. Our data suggest that SF HA is a relatively minor determinant of the kinetics of RISA clearance from the joint, and the changes in HA content seen in joint effusions are unlikely to confound interpretation of the concentration of marker molecules in SF.