The magnitude of articular cartilage destruction or repair in osteoarthritic (OA) joints has been deduced in some studies from the synovial fluid (SF) concentration of proteins derived from the extracellular matrix of the cartilage, without regard to the low grade synovitis that is often present in this disease. We examined the clearance kinetics of albumin, as a surrogate for cartilage derived proteins, from OA and control joints in an established canine model.
Twelve weeks after the left anterior cruciate ligament of 6 normal dogs was transected, 131I albumin (RISA) was injected into the contralateral (control) knee. Surface radioactivity was monitored for 7 h, and SF was then aspirated to determine the SF RISA concentration and leukocyte count, and calculate the volume of distribution (VD) and clearance of RISA. One week later, RISA was injected into the cruciate deficient knee and these measurements were repeated, then the intensity of synovial inflammation and severity of cartilage changes of OA in both knees were assessed.
Synovitis and articular cartilage ulceration were seen only in the cruciate-deficient OA knee, in which the mean SF leukocyte count (1570/mm3), thickness of the synovial intima (mean = 30 microns), and severity of synovial mononuclear cell infiltration (mean = 13,500 cells/mm2) significantly exceeded those in the contralateral knee (850/mm3, 13 microns, 1400 cells/mm2; p < or = 0.01 in each case). In each dog, RISA VD in the OA knee was higher than in the contralateral knee (mean = 9.2 +/- 3.6 and 3.7 +/- 0.9 ml, respectively; p = 0.008) and RISA clearance rate in the OA knee exceeded that in the contralateral knee (3.8 +/- 1.5 and 1.4 +/- 0.3 microliters/min, respectively; p = 0.009).
Accelerated clearance of protein from the OA joint with low grade synovitis could significantly affect the SF concentration of cartilage derived proteins. Therefore, inferences about the effect of a therapeutic agent on cartilage metabolism based upon changes in the concentration of a protein in serial samples of OA SF may be misleading unless protein clearance kinetics have been determined.