Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NF{kappa}B

Journal Article · Sun Jan 01 00:00:00 EST 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.09.016· OSTI ID:20775326

Eliseev, Roman A ^[1]; Schwarz, Edward M ^[1]; Zuscik, Michael J ^[1]; O'Keefe, Regis J ^[1]; Drissi, Hicham ^[1]; Rosier, Randy N ^[1]

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1. Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642 (United States)

The transcription factor NF{kappa}B is constitutively activated in various tumor cells where it promotes proliferation and represses apoptosis. The bone morphogenetic proteins (BMPs) delay cell proliferation and promote differentiation and apoptosis of bone cells through activation of Smad downstream effectors and via Smad-independent mechanisms. Thus, NF{kappa}B and BMP pathways play opposing roles in regulating osteoblastic cell fate. Here, we show that in osteosarcoma Saos2 osteoblasts, NF{kappa}B regulates the activity of the BMP/Smad signaling. Inhibition of NF{kappa}B by overexpression of mI{kappa}B leads to the induction of osteoblast differentiation. Saos2 cells overexpressing mI{kappa}B (Saos2-mI{kappa}B) exhibit higher expression of osteoblast phenotypic genes such as alkaline phosphatase, Runx2 and osteocalcin and are more responsive to BMP2 in comparison to wild-type cells (Saos2-wt) or empty vector infected controls (Saos2-EV). Furthermore, BMP-2 signaling and Smad phosphorylation are significantly increased in Saos2-mI{kappa}B cells in comparison to Saos2-EV cells. Inhibition of NF{kappa}B signaling in Saos2-mI{kappa}B cells is associated with decreased expression of the BMP signaling inhibitor Smad7. While gain of Smad7 function in Saos2-mI{kappa}B cells results in inhibition of BMP signaling, anti-sense knockdown of Smad7 in Saos2-EV cells leads to upregulation of BMP signaling. We therefore conclude that in osteosarcoma Saos2 cells, NF{kappa}B represses BMP/Smad signaling and BMP2-induced differentiation through Smad7.

• OSTI ID: 20775326
• Journal Information: Experimental Cell Research, Vol. 312, Issue 1; Other Information: DOI: 10.1016/j.yexcr.2005.09.016; PII: S0014-4827(05)00438-6; Copyright (c) 2005 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

Related Subjects

60 APPLIED LIFE SCIENCES
ALKALINE PHOSPHATASE
APOPTOSIS
BONE CELLS
CELL DIFFERENTIATION
CELL PROLIFERATION
OSTEOSARCOMAS
PHOSPHORYLATION
SKELETON
TRANSCRIPTION FACTORS
TUMOR CELLS