Antisense targeting of TGF-β1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells

Despite commonalities in signal transduction in osteoblasts from different species, the role of TGF-beta 1 on bone formation remains elusive. In particular, the role of autocrine TGF-beta 1 on human osteoblasts is largely unknown. Here we show the effect of TGF-beta 1 knock-down on the proliferation and differentiation of osteoblasts induced by BMP2. Treatment with antisense TGF-beta 1 moderately increased the rate of cell proliferation, which was completely reversed by the exogenous addition of TGF-beta 1. Notably, TGF-beta 1 blockade significantly enhanced BMP2-induced upregulation of mRNAs encoding osteopontin, type I collagen and Cbfa1, which was suppressed by exogenous TGF-beta 1. Moreover, TGF-beta 1 knock-down increased BMP2-induced phosphorylation of Smad1/5 as well as their nuclear import, which paralleled a reduction of inhibitory Smad6. These data suggest autocrine TGF-beta 1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5. (c) 2007 Elsevier Inc. All rights reserved.