PMID- 20004646
OWN - NLM
STAT- MEDLINE
DCOM- 20100315
LR  - 20100127
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 391
IP  - 1
DP  - 2010 Jan 1
TI  - Tumor necrosis factor-alpha increases alkaline phosphatase expression in vascular 
      smooth muscle cells via MSX2 induction.
PG  - 1087-92
LID - 10.1016/j.bbrc.2009.12.027 [doi]
AB  - Vascular calcification is implicated in many diseases including atherosclerosis 
      and diabetes. Tumor necrosis factor-alpha (TNF-alpha) has been shown to promote 
      vascular calcification both in vitro and in vivo. However, the molecular 
      mechanism of TNF-alpha-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-alpha-induced vascular calcification and to define the 
      regulatory mechanism of MSX2 induction in human vascular smooth muscle cells 
      (VSMCs). TNF-alpha 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-alpha 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-alpha-induced ALP expression. New protein synthesis was 
      dispensable for MSX2 induction by TNF-alpha, and the inhibition of NF-kappaB by 
      BAY-11-7082 or by dominant negative IkappaBalpha abolished the TNF-alpha-directed 
      induction of MSX2 expression. However, inhibition of NADPH oxidase did not affect 
      MSX2 expression. In conclusion, our study suggests that TNF-alpha directly 
      induces MSX2 expression through the NF-kappaB pathway, which in turn induces 
      expression of ALP, a key molecule in mineralization, in VSMCs.
CI  - Copyright 2009 Elsevier Inc. All rights reserved.
FAU - Lee, Hye-Lim
AU  - Lee HL
AD  - Department of Cell and Developmental Biology, School of Dentistry and Dental 
      Research Institute, Seoul National University, Seoul, Republic of Korea.
FAU - Woo, Kyung Mi
AU  - Woo KM
FAU - Ryoo, Hyun-Mo
AU  - Ryoo HM
FAU - Baek, Jeong-Hwa
AU  - Baek JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091214
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MSX2 protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/*biosynthesis
MH  - Calcinosis/*metabolism
MH  - Cells, Cultured
MH  - Homeodomain Proteins/*metabolism
MH  - Humans
MH  - Muscle, Smooth, Vascular/drug effects/*enzymology
MH  - Myocytes, Smooth Muscle/drug effects/enzymology
MH  - NF-kappa B/metabolism
MH  - Osteogenesis
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
EDAT- 2009/12/17 06:00
MHDA- 2010/03/17 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/12/01 00:00 [received]
PHST- 2009/12/07 00:00 [accepted]
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/03/17 06:00 [medline]
AID - S0006-291X(09)02400-0 [pii]
AID - 10.1016/j.bbrc.2009.12.027 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2010 Jan 1;391(1):1087-92. doi: 
      10.1016/j.bbrc.2009.12.027. Epub 2009 Dec 14.