title: Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum.
abstract: Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by calcified elastic fibers in cutaneous, ocular, and vascular tissues. PXE is caused by mutations in ABCC6, which encodes a protein of the ATP-driven organic anion transporter family. The inability of this transporter to secrete its substrate into the circulation is the likely cause of PXE. Vitamin K plays a role in the regulation of mineralization processes as a co-factor in the carboxylation of calcification inhibitors such as Matrix Gla Protein (MGP). Vitamin K precursor or a conjugated form has been proposed as potential substrate(s) for ABCC6. We investigated whether an enriched diet of vitamin K1 or vitamin K2 (MK4) could stop or slow the disease progression in Abcc6 (-/-) mice. Abcc6 (-/-) mice were placed on a diet of either vitamin K1 or MK4 at 5 or 100 mg/kg at prenatal, 3 weeks or 3 months of age. Disease progression was quantified by measuring the calcium content of one side of the mouse muzzle skin and histological staining for calcium of the opposing side. Raising the vitamin K1 or MK4 content of the diet increased the concentration of circulating MK4 in the serum. However, this increase did not significantly affect the MGP carboxylation status or reduce its abnormal abundance, the total calcium content or the pathologic calcification in the whiskers of the 3 treatment groups compared to controls. Our findings showed that raising the dietary intake of vitamin K1 or MK4 was not beneficial in the treatment of PXE and suggested that the availability of vitamin K may not be a limiting factor in this pathology.
authors: University of Hawai'i, Honolulu, Hawai'i, USA.
authors: Christopher
authors: C
authors: Brampton
authors: Yukiko
authors: Y
authors: Yamaguchi
authors: Olivier
authors: O
authors: Vanakker
authors: Lut
authors: L
authors: Van Laer
authors: Li-Hsieh
authors: LH
authors: Chen
authors: Manoj
authors: M
authors: Thakore
authors: Anne
authors: A
authors: De Paepe
authors: Viola
authors: V
authors: Pomozi
authors: Pál T
authors: PT
authors: Szabó
authors: Ludovic
authors: L
authors: Martin
authors: András
authors: A
authors: Váradi
authors: Olivier
authors: O
authors: Le Saux
references: Mol Cell Biol. 2005 Sep;25(18):8299-310
references: 16135817
references: Exp Dermatol. 2001 Aug;10(4):221-8
references: 11493310
references: J Mol Med (Berl). 2010 Feb;88(2):173-81
references: 19784827
references: J Histochem Cytochem. 2003 Jul;51(7):887-902
references: 12810839
references: Lab Invest. 2010 Jun;90(6):895-905
references: 20368697
references: J Nutr. 1992 Apr;122(4):953-8
references: 1552370
references: J Med Genet. 2005 Dec;42(12):881-92
references: 15894595
references: J Med Genet. 2007 Oct;44(10):621-8
references: 17617515
references: J Nutr. 1996 Feb;126(2):537-43
references: 8632229
references: Blood. 2007 Apr 15;109(8):3279-83
references: 17158229
references: Nat Genet. 2000 Jun;25(2):228-31
references: 10835643
references: Biochem J. 1990 Mar 15;266(3):625-36
references: 2183788
references: Nat Genet. 2000 Jun;25(2):223-7
references: 10835642
references: Blood. 2007 Apr 1;109(7):2823-31
references: 17138823
references: J Biol Chem. 2008 Apr 25;283(17):11270-9
references: 18083713
references: J Invest Dermatol. 2005 Nov;125(5):900-5
references: 16297187
references: Nat Genet. 1999 Feb;21(2):150-1
references: 9988260
references: Bone. 1995 Feb;16(2):179-84
references: 7756045
references: Proc Natl Acad Sci U S A. 2000 May 23;97(11):6001-6
references: 10811882
references: Lab Invest. 2002 Apr;82(4):515-8
references: 11950908
references: Hum Mol Genet. 2005 Jul 1;14(13):1763-73
references: 15888484
references: J Nutr. 2004 Nov;134(11):3100-5
references: 15514282
references: J Invest Dermatol. 2007 Mar;127(3):581-7
references: 17110937
references: J Histochem Cytochem. 1958 Jan;6(1):22-42
references: 13514045
references: J Vasc Res. 2003 Nov-Dec;40(6):531-7
references: 14654717
references: Biochem Biophys Res Commun. 2007 Dec 14;364(2):208-13
references: 17942075
references: J Invest Dermatol. 2007 Jun;127(6):1392-402
references: 17273159
references: Cancer Res. 1999 Jan 1;59(1):175-82
references: 9892204
references: Ann Dermatol Venereol. 2001 Sep;128(8-9):943-6
references: 11590353
references: Trends Mol Med. 2001 Jan;7(1):13-7
references: 11427982
references: J Biol Chem. 2002 May 10;277(19):16860-7
references: 11880368
references: Lab Invest. 2007 Oct;87(10):998-1008
references: 17724449
references: Acta Paediatr. 1998 Sep;87(9):960-2
references: 9764891
references: Cell Cycle. 2008 Jun 1;7(11):1575-9
references: 18469514
references: Lancet. 1995 Jan 28;345(8944):229-34
references: 7823718
references: Curr Opin Clin Nutr Metab Care. 2000 Nov;3(6):433-8
references: 11085828