MARKERS OF CARTILAGE AND SYNOVIAL METABOLISM IN JOINT FLUID AND SERUMOF PATIENTS WITH CHONDROMALACIA OF THE PATELLA

Objective: To further our understanding of the pathogenesis of chondro malacia of the patella (CM), we have studied the release into knee joi nt fluid and serum, obtained from patients with CM, of molecules assoc iated with the metabolism of joint cartilage matrix and synovium. Meth ods: Interleukin-l alpha (IL-1 alpha), interleukin-l beta (IL-1 beta), interleukin-6 (IL-6), stromelysin-l (MMP-3), interstitial collagenase (MMP-1), tissue inhibitor for metalloproteinases-l (TIMP-1), phosphol ipase activity A(2) (PLA(2)), hyaluronan (HA), aggrecan fragments (AGN ) and antigenic keratan sulfate (KS) were quantified in knee joint lav age fluid from 96 patients with CM; KS and HA also was measured in ser um. Chondromalacia was graded on a scale of I to IV according to Outer bridge (1961). The histopathology of the synovial membrane close to th e patellofemoral joint was evaluated. Control samples were obtained fr om nine patients with knee pain presenting with arthroscopically norma l knee joints. Results: The concentrations of MMP-3, MMP-1 and TIMP-1 proteins in joint lavage fluid were increased in advanced (grade IV) C M, compared with controls. Levels of MMP-1 in lavage fluid correlated with the severity of CM (r = 0.38, P < 0.01) and MMP-1 and MMP-3 conce ntrations correlated with each other (r = 0.45, P < 0.001). TIMP-1 was elevated in grade IV CM compared with grades II and III CM (P < 0.02, P < 0.01). Interleukins (IL-1 alpha, IL-1 beta and IL-6) showed no si gnificant change in CM. The lavage fluid level of PLA(2) increased wit h the severity of CM (r = 0.40, P < 0.001). Serum KS was higher in CM IV than in controls (P = 0.05), while lavage fluid KS concentration wa s elevated in CM I (P = 0.04). There were no differences in the lavage fluid levels of AGN and HA between the different study groups. Synovi um showed slight or moderate histological signs of inflammation in 9% of CM patients. Conclusion: The changes in the release and activity of these marker molecules from serum and synovial fluid may reflect chan ges in the metabolism of articular cartilage and synovium in CM, that are consistent with those observed in early-stage tibiofemoral cartila ge changes in OA.