Expression of c-fos gene inhibits proteoglycan synthesis in transfected chondrocyte.
The effect of expression of c-fos gene on proteoglycan synthesis, one of the important markers of cartilage metabolism, was examined by introducing the c-fos DNA into HCS 2/8 chondrocytes. The [35S]sulfate incorporation into proteoglycan was decreased in the c-fos transfectants expressing exogenous c-fos mRNA, when compared to a control transfectant. A significant increase in transcription of MMP-3 with the suppressed transcription of aggrecan and TIMP-1 were also observed in the c-fos transfectants. Moreover, analysis of the effect of AP-1 proteins on the collagenase and TIMP-1 promoters in gastric carcinoma KKLS cells revealed that c-Fos combined with any of the Jun-related proteins failed to stimulate the TIMP-1 promoter, though collagenase promoter was effectively activated by any Fos/Jun-related protein heterocomplex. These findings indicate that the c-fos expression may govern the cartilage metabolism and hence may play an important role in the pathogenesis of joint destruction in arthritis.
Tsuji
M
M
Tokyo Institute for Immunopharmacology, Japan.
Funahashi
S
S
Takigawa
M
M
Seiki
M
M
Fujii
K
K
Yoshida
T
T
D001483:Base Sequence; D001859:Bone Neoplasms; D002104:Cadmium / Q000494:pharmacology; D002356:Cartilage; D002460:Cell Line; D002813:Chondrosarcoma; D002852:Chromatography, Ion Exchange; D017364:Collagenases / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D013274:Stomach Neoplasms; D019714:Tissue Inhibitor of Metalloproteinases; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D011509:Proteoglycans; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D018808:Transcription Factor AP-1; D002104:Cadmium; D017364:Collagenases