Enhanced expression of fibronectin by cmd/cmd chondrocytes and its modulation by exogenously added proteoglycan.
Cartilage matrix deficiency (cmd/cmd) in mice is a genetic disorder associated with the failure of chondrocytes to synthesize the core protein of cartilage proteoglycan monomer (cartilage-PG). Immunohistochemical and biochemical analyses revealed enhanced accumulation of fibronectin in culture of cmd/cmd chondrocytes as well as in mutant cartilage tissue in vivo. Purified cartilage-PG, when added exogenously to a culture of cmd/cmd chondrocytes, caused a reduction in abnormal accumulation of fibronectin over several subsequent days of culturing. Using a fibronectin cDNA probe, we showed that, on the basis of total RNA, the fibronectin mRNA level was four or eight times higher in cmd/cmd chondrocytes than in the normal. The level of fibronectin mRNA in cmd/cmd cells was lowered by culturing the cells in the presence of added cartilage-PG. These findings suggest that the abnormal accumulation of fibronectin in the mutant cell culture is primarily due to elevation of fibronectin mRNA level, and that cartilage-PG in the extracellular matrix may affect the regulation of fibronectin biosynthesis at the steady-state level of mRNA.
Tsukahara
T
T
Institute for Molecular Science of Medicine, Aichi Medical University, Japan.
Okamura
M
M
Suzuki
S
S
Iwata
H
H
Miura
T
T
Kimata
K
K
D000818:Animals; D002357:Cartilage Diseases / Q000235:genetics* / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects; D005353:Fibronectins / Q000032:analysis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D011509:Proteoglycans / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis
D005353:Fibronectins; D011509:Proteoglycans; D012333:RNA, Messenger