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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Bibliographic Details
Published in:Experimental cell research 2007-04, Vol.313 (7), p.1415
Main Authors: Zhong-Jian, Shen, Kim, Sang Kook, Do Youn Jun, Park, Wan, Young Ho Kim, Malter, James S, Moon, Byung Jo
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Antagonist drugs
Bones
CELL PROLIFERATION
Cellular biology
COLLAGEN
CONNECTIVE TISSUE CELLS
OLIGONUCLEOTIDES
PHOSPHORYLATION
Signal transduction
SKELETON
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Summary: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]
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2007.01.014