Is pro-matrix metalloproteinase-3 a marker for posttraumatic cartilage degradation?
OBJECTIVE
Since the development of posttraumatic osteoarthritis (OA) is a relatively slow process, estimation of OA risk would be of value with regard to chondroprotective measures and medication. In this study we investigated the significance of pro-matrixmetalloproteinase-3 (proMMP-3) for this purpose.


METHODS
Synovial fluid (SF) and serum samples were collected from 259 patients of our trauma clinic at the time of arthroscopy. The extent of cartilage damage was assessed according to the Outerbridge-score. ProMMP-3 levels in SF and serum were determined by enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody. Additionally we determined SF and serum levels of total MMP-3 and COMP levels as well as TIMP-1 and -2 concentrations in 40 randomly selected patients by ELISA.


RESULTS
Serum proMMP-3 levels of the total cohort were markedly increased compared to healthy controls (P<0.007). The comparison of serum and SF lavage proMMP-3 concentrations showed a significant correlation (r(s)=0.41, P<0.0001), however, only 26% of the investigated samples were increased above normal ranges. The grade of cartilage damage did not correlate with enzyme concentration neither in patients' serum nor in SF samples. ProMMP-3 SF concentration was increased early after trauma. Furthermore, proMMP-3 correlated significantly with total MMP-3 serum and SF levels as well as COMP SF levels.


CONCLUSIONS
The measurement of proMMP-3 in serum or SF did not reflect the present cartilage damage and thus appears to have only minor potential for clinical use, but it should be considered for longitudinal studies, since it may reflect a risk for cartilage degradation in a subset of patients.
Bobacz
K
K
Department of Internal Medicine III, Division of Rheumatology, University of Vienna, Vienna, Austria.
Maier
R
R
Fialka
C
C
Ekhart
H
H
Woloszczuk
W
W
Geyer
G
G
Erlacher
L
L
Smolen
J
J
Graninger
W B
WB
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002357:Cartilage Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000473:pathology*; D004792:Enzyme Precursors / Q000032:analysis* / Q000097:blood; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007718:Knee Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D064235:Matrilin Proteins; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D008666:Metalloendopeptidases / Q000032:analysis* / Q000097:blood; D008875:Middle Aged; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis
D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D004792:Enzyme Precursors; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D008666:Metalloendopeptidases; C048047:prostromelysin; D019278:Matrix Metalloproteinase 3