PMID- 22287655
OWN - NLM
STAT- MEDLINE
DCOM- 20121207
LR  - 20161125
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 27
IP  - 5
DP  - 2012 May
TI  - Vitamin D receptor activators inhibit vascular smooth muscle cell mineralization 
      induced by phosphate and TNF-alpha.
PG  - 1800-6
LID - 10.1093/ndt/gfr758 [doi]
AB  - BACKGROUND: Vascular calcification is a highly regulated process. Tumor necrosis 
      factor-alpha (TNF-alpha) has been shown to accelerate the highly regulated osteogenic 
      process in vascular smooth muscle cells (VSMCs). Vitamin D receptor activators 
      (VDRAs) have been associated with beneficial cardiovascular outcomes in patients 
      with chronic kidney disease. We examined whether maxacalcitol, a vitamin D(3) 
      analog, exhibits a suppressive effect on VSMC mineralization induced by phosphate 
      and TNF-alpha. METHODS: Human VSMCs were treated with either vehicle, maxacalcitol 
      (10(-9) to 10(-7) M), or calcitriol (10(-9) to 10(-7) M) in 2.5 mM of phosphate 
      media with TNF-alpha (1 ng/mL) for 9 days. VSMC mineralization was determined and 
      expression of genes associated with the osteogenic process was examined by 
      real-time reverse transcription-polymerase chain reaction. Expression of matrix 
      metalloproteinase-2 (MMP-2) messenger RNA (mRNA) in VSMCs and MMP-2 protein in 
      media was also analyzed. RESULTS: Vehicle-treated VSMCs exhibited massive 
      mineralization, which was inhibited by maxacalcitol in a concentration-dependent 
      manner. Calcitriol also inhibited the mineralization. While vehicle-treated VSMCs 
      exhibited increased mRNA expression of genes associated with the osteogenic 
      process (Cbfa1/Runx2 and osteocalcin) compared with VSMCs grown in normal media 
      without TNF-alpha (control), maxacalcitol and calcitriol suppressed the increase in 
      mRNA species. Furthermore, vehicle-treated VSMCs exhibited increased MMP-2 mRNA 
      and protein in the media that were suppressed notably by maxacalcitol. 
      CONCLUSIONS: Both the VDRAs abrogated the acceleration of the osteogenic process 
      induced by phosphate and TNF-alpha in VSMCs, which was linked to inhibition of 
      mineralization in VSMCs. MMP-2 blockade by VDRAs may contribute to an inhibitory 
      effect on vascular calcification.
FAU - Aoshima, Yumie
AU  - Aoshima Y
AD  - Division of Nephrology, Department of Medicine, Showa University School of 
      Medicine, Tokyo, Japan.
FAU - Mizobuchi, Masahide
AU  - Mizobuchi M
FAU - Ogata, Hiroaki
AU  - Ogata H
FAU - Kumata, Chiaki
AU  - Kumata C
FAU - Nakazawa, Ai
AU  - Nakazawa A
FAU - Kondo, Fumiko
AU  - Kondo F
FAU - Ono, Naoko
AU  - Ono N
FAU - Koiwa, Fumihiko
AU  - Koiwa F
FAU - Kinugasa, Eriko
AU  - Kinugasa E
FAU - Akizawa, Tadao
AU  - Akizawa T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120128
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Phosphates)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1406-16-2 (Vitamin D)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - FXC9231JVH (Calcitriol)
RN  - N2UJM5NBF6 (maxacalcitol)
SB  - IM
CIN - Nephrol Dial Transplant. 2012 May;27(5):1704-7. PMID: 22431706
MH  - Calcitriol/*analogs & derivatives/pharmacology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Muscle, Smooth, Vascular/cytology/*drug effects/*metabolism
MH  - Osteogenesis/drug effects/physiology
MH  - Phosphates/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Calcitriol/*drug effects/physiology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vascular Calcification/metabolism
MH  - Vitamin D/analogs & derivatives
EDAT- 2012/01/31 06:00
MHDA- 2012/12/12 06:00
CRDT- 2012/01/31 06:00
PHST- 2012/01/31 06:00 [entrez]
PHST- 2012/01/31 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
AID - gfr758 [pii]
AID - 10.1093/ndt/gfr758 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2012 May;27(5):1800-6. doi: 10.1093/ndt/gfr758. Epub 
      2012 Jan 28.