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

Zhong Jian Shen, Sang Kook Kim, Do Youn Jun, Wan Park, Young Ho Kim, James S. Malter, Byung Jo Moon

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Despite commonalities in signal transduction in osteoblasts from different species, the role of TGF-β1 on bone formation remains elusive. In particular, the role of autocrine TGF-β1 on human osteoblasts is largely unknown. Here we show the effect of TGF-β1 knock-down on the proliferation and differentiation of osteoblasts induced by BMP2. Treatment with antisense TGF-β1 moderately increased the rate of cell proliferation, which was completely reversed by the exogenous addition of TGF-β1. Notably, TGF-β1 blockade significantly enhanced BMP2-induced upregulation of mRNAs encoding osteopontin, type I collagen and Cbfa1, which was suppressed by exogenous TGF-β1. Moreover, TGF-β1 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-β1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5.

Original languageEnglish (US)
Pages (from-to)1415-1425
Number of pages11
JournalExperimental Cell Research
Volume313
Issue number7
DOIs
StatePublished - Apr 15 2007

Keywords

  • Antisense oligonucleotides
  • BMP
  • Bone
  • Differentiation
  • Osteoblasts
  • Proliferation
  • Smad
  • TGF

ASJC Scopus subject areas

  • Cell Biology

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