FIG. 8.

Modulation of TGF signaling for simultaneous cartilaginous and mineralized matrices in one culture well. Left: On scaffold with NT cells, TGFβ3 binds to the receptor complex and phosphorylates SMAD2 and SMAD3. Phosphorylated SMAD2/3 binds to SMAD4, translocates into the nucleus and forms a complex with respective transcription factors to turn on chondrogenic genes. Top right: On scaffold with scrambled shRNA with RUNX2-transduced cells, TGF signaling phosphorylates SMAD3, which translocates into the nucleus and recruit HDAC4/5 to the promoters of RUNX2 and RUNX2 downstream targets, repressing their transcriptions. Bottom right: On scaffold with SMAD3 shRNA with RUNX2-transduced cells, SMAD3 shRNA is expressed, and thus degrades SMAD3 mRNA or inhibits its translation. This leads to de-repression at the promoters of RUNX2 and RUNX2 downstream targets, activating their expression. [*] Adapted from.⁴⁷ TGF, transforming growth factor. Color images available online at www.liebertpub.com/tea