Markers of cartilage and synovial metabolism in joint fluid and serum of patients with chondromalacia of the patella.
OBJECTIVE
To further our understanding of the pathogenesis of chondromalacia of the patella (CM), we have studied the release into knee joint fluid and serum, obtained from patients with CM, of molecules associated with the metabolism of joint cartilage matrix and synovium.


METHODS
Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), stromelysin-1 (MMP-3), interstitial collagenase (MMP-1), tissue inhibitor for metalloproteinases-1 (TIMP-1), phospholipase activity A2 (PLA2), hyaluronan (HA), aggrecan fragments (AGN) and antigenic keratan sulfate (KS) were quantified in knee joint lavage fluid from 96 patients with CM; KS and HA also was measured in serum. Chondromalacia was graded on a scale of I to IV according to Outerbridge (1961). The histopathology of the synovial membrane close to the patellofemoral joint was evaluated. Control samples were obtained from nine patients with knee pain presenting with arthroscopically normal knee joints.


RESULTS
The concentrations of MMP-3, MMP-1 and TIMP-1 proteins in joint lavage fluid were increased in advanced (grade IV) CM, 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 concentrations 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 significant change in CM. The lavage fluid level of PLA2 increased with 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 was 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. Synovium showed slight or moderate histological signs of inflammation in 9% of CM patients.


CONCLUSIONS
The changes in the release and activity of these marker molecules from serum and synovial fluid may reflect changes in the metabolism of articular cartilage and synovium in CM, that are consistent with those observed in early-stage tibiofemoral cartilage changes in OA.
Department of Surgery, Kuopio University Hospital, Finland.
U
U
Väätäinen
L S
LS
Lohmander
E
E
Thonar
T
T
Hongisto
U
U
Agren
S
S
Rönkkö
H
H
Jaroma
V M
VM
Kosma
M
M
Tammi
I
I
Kiviranta
D000328:Adult; D053674:Aggrecans; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002357:Cartilage Diseases / Q000097:blood / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D017364:Collagenases / Q000032:analysis; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007632:Keratan Sulfate / Q000032:analysis; D007719:Knee Joint; D037181:Lectins, C-Type; D008297:Male; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D010741:Phospholipases A / Q000032:analysis; D054467:Phospholipases A2; D011480:Protease Inhibitors / Q000032:analysis; D011509:Proteoglycans / Q000032:analysis; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
D053674:Aggrecans; D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D037181:Lectins, C-Type; D011480:Protease Inhibitors; D011509:Proteoglycans; D019715:Tissue Inhibitor of Metalloproteinase-1; D006820:Hyaluronic Acid; D007632:Keratan Sulfate; D010741:Phospholipases A; D054467:Phospholipases A2; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1