Transforming growth factor-beta modulates the expression of osteoblast and chondroblast phenotypes in vitro.
Transforming growth factor beta (TGF-beta) has been shown to induce chondrogenesis by embryonic rat mesenchymal cells (Seyedin et al., J. Biol. Chem., 261: 5693, 1986). Here we report the effects of bovine TGF-beta on the phenotypic expression of differentiated primary rat osteoblastic and chondroblastic cells. Culture of rat calvarial osteoblasts with TGF-beta resulted in a dose and time-dependent decrease in alkaline phosphatase activity. Levels of alkaline phosphatase were reduced to less than 10% of control values by 0.4 nM TGF-beta. The decrease became apparent after 24 hours and reached a maximum by 72 hours. Similarly, treatment of chondroblasts with 0.4 nM TGF-beta resulted in decreased production of cartilage-specific macromolecules: type II collagen and cartilage proteoglycan. Both cell types exhibited dramatic changes in cell shape after treatment with TGF-beta. Modulation of these differentiated markers by TGF-beta could be mimicked, in part, by addition of fibronectin. Addition of dihydrocytochalasin B blocked the inhibition of phenotypic expression by TGF-beta. These results indicate that TGF-beta inhibits phenotypic expression by osteoblasts and chondroblasts in vitro and suggest that this activity of TGF-beta may be mediated through interactions between the extracellular matrix and cytoskeletal elements.
Rosen
D M
DM
Connective Tissue Research Laboratories, Collagen Corporation, Palo Alto, California 94303.
Stempien
S A
SA
Thompson
A Y
AY
Seyedin
S M
SM
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003571:Cytochalasin B / Q000031:analogs & derivatives / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D005353:Fibronectins / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010641:Phenotype; D014176:Protein Biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015291:Transforming Growth Factors
D005353:Fibronectins; D010455:Peptides; D011509:Proteoglycans; D012333:RNA, Messenger; C024794:dihydrocytochalasin B; D003571:Cytochalasin B; D015291:Transforming Growth Factors; D003094:Collagen; D000469:Alkaline Phosphatase