DIFFERENTIAL EXPRESSION OF MESSENGER-RNAS FOR ENDOPEPTIDASES IN PHENOTYPICALLY MODULATED (DEDIFFERENTIATED) HUMAN ARTICULAR CHONDROCYTES

Human articular chondrocytes modulated away from their original phenot ype by serial subcultures in monolayer differentially express mRNAs fo r endopeptidases. The mRNAs for the cathepsins B and L are extremely l ow in differentiated cells, but are soon expressed in parallel with th e loss of the differentiated state, In contrast, the mRNA for collagen ase-1 is strongly expressed by differentiated chondrocytes and decline s 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 endop eptidases in a was that markedly differs from that induced by cytokine s, 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 endopeptidase s. (C) 1997 Federation of European Biochemical Societies.