The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Unique and redundant roles of Smad3 in TGF-beta-mediated regulation of long bone development in organ culture.

The most well-characterized intracellular signaling molecules for transforming growth factor-beta (TGF-beta) are the Smads. R-Smads interact with and are phosphorylated directly by the TGF-beta type I receptor. Phosphorylated R-Smads can then associate with Smad4, translocate to the nucleus and regulate transcription. Specific R-Smads transduce distinct signals for members of the TGF-beta superfamily. Smad2 and -3 mediate signaling by TGF-beta/ activin, whereas Smad1, -5, and -8 mediate bone morphogenetic protein signaling. TGF-beta inhibits proliferation and hypertrophic differentiation in metatarsal organ cultures by a perichondrium-dependent mechanism. To determine the mechanism of TGF-beta signaling in the perichondrium, we tested the hypothesis that TGF-beta-restricted Smad2 and Smad3 regulate chondrocyte proliferation and differentiation in embryonic metatarsal organ cultures. Perichondrium was infected with adenoviruses containing dominant-negative forms of Smad2 (Ad-Smad2-3SA) and Smad3 (Ad-Smad3 Delta C). Proliferation and differentiation were measured in response to treatment with TGF-beta 1. Results were compared with control bones infected with a beta-galactosidase reporter virus (Ad-beta-gal). Infection with Ad-Smad2-3SA completely blocked the effects of TGF-beta 1 on metatarsal development while Ad-Smad3 Delta C only partially blocked TGF-beta 1 effects. To further characterize the role of Smad3 in long bone development, TGF-beta 1 responsiveness in cultures from Smad3(+/+) and Smad3(ex8/ex8) mice were compared. Loss of Smad3 only partially blocked the effects of TGF-beta1 on differentiation. In contrast, the effects of TGF-beta 1 on chondrocyte proliferation were blocked completely. We conclude that Smad2 signaling in the perichondrium can compensate for the loss of Smad3 to regulate inhibition of hypertrophic differentiation; however, Smad3 is required for TGF-beta 1-mediated effects on proliferation.[1]

References

 
WikiGenes - Universities