Differential expression of mRNAs for endopeptidases in phenotypically modulated ('dedifferentiated') human articular...

Human articular chondrocytes modulated away from their original phenotype by serial subcultures in monolayer differentially express mRNAs for endopeptidases. The mRNAs for the cathepsins B and L are extremely low in differentiated cells, but are soon expressed in parallel with the loss of the differentiated state. In contrast, the mRNA for collagenase-1 is strongly expressed by differentiated chondrocytes and declines rapidly following phenotypic modulation. The mRNA for stromelysin-1 and the tissue inhibitor of metalloproteinases-2 is high and does not appreciably change after modulation. Chondrocyte activation induced by alteration of its original phenotype leads to the expression of endopeptidases in a way that markedly differs from that induced by cytokines. The results are relevant to cartilage catabolism in osteoarthritis and suggest a prominent role of fibroblastic metaplasia on the part of the chondrocytes as a mechanism of expressing catabolic endopeptidases.