Transforming growth factor-beta inhibits nephronectin-induced osteoblast differentiation.
We used cDNA microarray to identify transforming growth factor beta (TGF-beta) responsive target genes during osteoblast development and found that nephronectin (Npnt) is one such gene that is significantly down-regulated. Here we report the role of TGF-beta in regulating Npnt-mediated osteoblast differentiation. We found that the effect of TGF-beta on Npnt expression is associated with a change in cell morphology in a dose-dependent manner. Npnt-induced osteoblast differentiation was also inhibited by TGF-beta, which changed cell morphology from cuboidal to fibroblastic, an indication that osteoblast differentiation was disrupted. Furthermore, TGF-beta inhibited differentiation of osteoblasts transfected with various truncated Npnt constructs, suggesting that TGF-beta can exert a down-stream effect on Npnt function. Our results suggest that TGF-beta can inhibit osteoblast differentiation through various mechanisms.
Fang
Ling
L
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
Kahai
Shireen
S
Yang
Weining
W
He
Chengyan
C
Seth
Arun
A
Peng
Chun
C
Yang
Burton B
BB
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D043264:Phosphodiesterase I / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; C432915:nephronectin; D043264:Phosphodiesterase I