Antisense targeting of TGF-[beta]1 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-beta1 on bone formation remains elusive. In particular, the role of autocrine TGF-beta1 on human osteoblasts is largely unknown. Here we show the effect of TGF-beta1 knock-down on the proliferation an...
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Veröffentlicht in: | Experimental cell research 2007-04, Vol.313 (7), p.1415 |
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Sprache: | eng |
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Zusammenfassung: | Despite commonalities in signal transduction in osteoblasts from different species, the role of TGF-beta1 on bone formation remains elusive. In particular, the role of autocrine TGF-beta1 on human osteoblasts is largely unknown. Here we show the effect of TGF-beta1 knock-down on the proliferation and differentiation of osteoblasts induced by BMP2. Treatment with antisense TGF-beta1 moderately increased the rate of cell proliferation, which was completely reversed by the exogenous addition of TGF-beta1. Notably, TGF-beta1 blockade significantly enhanced BMP2-induced upregulation of mRNAs encoding osteopontin, type I collagen and Cbfa1, which was suppressed by exogenous TGF-beta1. Moreover, TGF-beta1 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-beta1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5. [PUBLICATION ABSTRACT] |
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ISSN: | 0014-4827 1090-2422 |
DOI: | 10.1016/j.yexcr.2007.01.014 |