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Tumor necrosis factor-α increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction

Cited 80 time in Web of Science Cited 85 time in Scopus
Authors
Lee, Hye-Lim; Woo, Kyung Mi; Ryoo, Hyun-Mo; Baek, Jeong-Hwa
Issue Date
2010-01
Publisher
Elsevier
Citation
Biochemical and Biophysical Research Communications 2010;391:1087-1092
Keywords
Vascular smooth muscle cellsTumor necrosis factor-αMSX2NF-κBAlkaline phosphatase
Abstract
Vascular calcification is implicated in many diseases including atherosclerosis and diabetes. Tumor necrosis factor-α (TNF-α) has been shown to promote vascular calcification both in vitro and in vivo. However, the molecular mechanism of TNF-α-mediated vascular calcification has not yet been fully defined. Therefore, in this study, we aimed to investigate whether MSX2 acts as a crucial regulator in TNF-α-induced vascular calcification and to define the regulatory mechanism of MSX2 induction in human vascular smooth muscle cells (VSMCs). TNF-α increased the expression of osteogenic marker genes including RUNX2, osterix, alkaline phosphatase (ALP), and bone sialoprotein, and it also promoted matrix mineralization in VSMCs. In addition, TNF-α enhanced MSX2 expression in a dose- and time-dependent manner. MSX2 over-expression alone induced ALP expression, whereas knockdown of MSX2 with small interfering RNA completely blocked TNF-α-induced ALP expression. New protein synthesis was dispensable for MSX2 induction by TNF-α, and the inhibition of NF-κB by BAY-11-7082 or by dominant negative IκBα abolished the TNF-α-directed induction of MSX2 expression. However, inhibition of NADPH oxidase did not affect MSX2 expression. In conclusion, our study suggests that TNF-α directly induces MSX2 expression through the NF-κB pathway, which in turn induces expression of ALP, a key molecule in mineralization, in VSMCs.
ISSN
0006-291X
Language
English
URI
https://hdl.handle.net/10371/74145
DOI
https://doi.org/10.1016/j.bbrc.2009.12.027
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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