Metalloproteinases, tissue inhibitor, and proteoglycan fragments in knee synovial fluid in human osteoarthritis.
OBJECTIVE
To determine the concentrations of human stromelysin-1, collagenase, tissue inhibitor of metalloproteinases (TIMP), and proteoglycan fragments in knee synovial fluid in patients with injury to the meniscus or anterior cruciate ligament, posttraumatic osteoarthritis, primary osteoarthritis, or pyrophosphate arthritis.


METHODS
Synovial fluid samples were collected from patients with knee disease diagnosed arthroscopically and radiologically. Concentrations of stromelysin-1, collagenase, and TIMP-1 were determined by sandwich immunoassay, using monoclonal and polyclonal antibodies. Fragments of cartilage proteoglycan containing the chondroitin sulfate-binding region were determined by immunoassay with a polyclonal antibody.


RESULTS
Average concentrations of metalloproteinases, TIMP, and proteoglycan fragments in joint fluid were significantly elevated in patients from all disease groups as compared with volunteers with healthy knees (reference group). Stromelysin concentrations in disease groups averaged 15-45 times that of the reference group. The molar ratios between stromelysin and collagenase varied between 10 and 150. The molar ratio between total stromelysin and free TIMP was 0.5 in the reference group and between 1.6 and 5.3 in the disease groups.


CONCLUSIONS
Stromelysin concentration in joint fluid is a parameter that distinguishes diseased joints from healthy joints, with a sensitivity of 84% and a specificity of 90%. The high concentrations of metalloproteinase relative to TIMP in joint fluid from patients with the conditions studied may be associated with cartilage matrix degradation in these arthritides.
Lohmander
L S
LS
Department of Orthopedics, University Hospital, Lund, Sweden.
Hoerrner
L A
LA
Lark
M W
MW
D000328:Adult; D000368:Aged; D003953:Diagnosis-Related Groups; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007596:Joints / Q000737:chemistry; D007719:Knee Joint; D007958:Leukocyte Count; D008297:Male; D019278:Matrix Metalloproteinase 3; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000032:analysis*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis*; D011509:Proteoglycans / Q000032:analysis*; D013582:Synovial Fluid / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D010446:Peptide Fragments; D011509:Proteoglycans; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3