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Ann Rheum Dis. Sep 1997; 56(9): 542–549.
PMCID: PMC1752435

Gene expression of matrix metalloproteinases 1, 3, and 9 by chondrocytes in osteoarthritic human knee articular cartilage is zone and grade specific


OBJECTIVES—Matrix metalloproteinases (MMPs) are thought to be major mediators of cartilage destruction. Osteoarthritis (OA) is characterised by cartilage degradation. This study explores gene expression of three MMPs in articular chondrocytes during the histological development of the cartilage lesion of OA.
METHODS—Biopsy specimens of human normal and OA cartilage, classified into four grades on the basis of histology, were probed for MMPs 1, 3, and 9 using 35S-labelled cDNA probes. The signal was measured at four different depths (zones) using an automated image analyser and compared with signal from sections probed with λDNA. Rheumatoid synovium was used as a positive control for MMP gene expression.
RESULTS—Rheumatoid tissue contained mRNA for all three MMPs. Expression in chondrocytes varied with the depth of the chondrocyte in the cartilage and the histomorphological extent of the OA changes. There was no detectable mRNA signal for these three MMPs in normal cartilage. In general, in OA, MMP-1 gene expression was greatest in the superficial cartilage in established disease. By contrast mRNAs for MMP-3 and 9 were expressed deeper in the cartilage, MMP-9 early in disease and MMP-3 with a biphasic pattern in early and late stage disease, most pronounced in the latter. This was a consequence of differential expression in single cells and chondrocyte clusters in late disease.
CONCLUSION—The data indicate that expression of genes for MMPs 1, 3, and 9 is differentially regulated in human articular chondrocytes and, in individual cells, is related to the depth of the chondrocyte below the cartilage surface and the nature and extent of the cartilage lesion.

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Figures and Tables

Figure 1
Each diagram shows the distribution and amount of a metalloproteinase mRNA signal in articular cartilage in the various zones and grades of cartilage damage. The (S−N)/N ratio is represented by the density of shading of the box and by the numbers ...
Figure 2
Examples of ISH reaction in articular cartilage. (A) Low power light photomicrograph of zones 2, 3, and 4 grade 3 reacted for MMP-1. The subchondral bone is in the bottom right and the articular surface bearing a small ...

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