Fig. 10.

Overexpression of LMP-1 causes nuclear accumulation of Smad4 protein in hMSCs. LMP-1 overexpression increases the efficacy of BMP-2 to induce nuclear translocation of Smad4 in hMSCs as measured in western blot. Human MSCs were treated with or without Ad5F35 LMP-1 (5 pfu/cell) and rhBMP-2 (100 ng/ml) for 8 h as described in “Materials and methods.” We observed a twofold increase in the amount of Smad4 detected in LMP-1 overexpressed cells compared with control cells. The phosphorylated receptor Smads1, 5 or 8 oligomerize with Smad4, enter the nucleus and induce osteogenic genes in the BMP pathway. An increase in nuclear Smad4 is an indicator of enhancement of this pathway