title: Differential expression of mRNAs for endopeptidases in phenotypically modulated ('dedifferentiated') human articular chondrocytes.
abstract: 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.
authors.affiliation: University Hospital, Department of Rheumatology, Zurich, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Kostoulas
authors.forename: A
authors.initials: A
authors.lastname: Lang
authors.forename: B
authors.initials: B
authors.lastname: Trueb
authors.forename: A
authors.initials: A
authors.lastname: Baici
mesh_terms: D000328:Adult; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology*; D002401:Cathepsin B / Q000235:genetics; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D019716:Tissue Inhibitor of Metalloproteinase-2
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; D017364:Collagenases; D019278:Matrix Metalloproteinase 3