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Title: Antisense targeting of TGF-{beta}1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells

Journal Article · · Experimental Cell Research
 [1];  [2];  [2];  [3];  [3];  [4];  [5]
  1. Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701 (Korea, Republic of) and Department of Pathology and Laboratory Medicine, Waisman Center for Developmental Disabilities, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 (United States)
  2. Institute of Genetic Engineering, Kyungpook National University, Taegu 702-701 (Korea, Republic of)
  3. Department of Microbiology, College of Natural Sciences, Kyungpook National University, Taegu 702-701 (Korea, Republic of)
  4. Department of pathology and Laboratory Medicine, Waisman Center for Developmental Disabilities, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, 53705 (United States)
  5. Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702-701 (Korea, Republic of)

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.

OSTI ID:
20972140
Journal Information:
Experimental Cell Research, Vol. 313, Issue 7; Other Information: DOI: 10.1016/j.yexcr.2007.01.014; PII: S0014-4827(07)00037-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
Country of Publication:
United States
Language:
English

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