Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum

Christopher Brampton, Yukiko Yamaguchi, Olivier Vanakker, Lut Van Laer, Li Hsieh Chen, Manoj Thakore, Anne De Paepe, Viola Pomozi, P. Szabó, Ludovic Martin, A. Váradi, Olivier Le Saux

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1810-1820
Number of pages11
JournalCell Cycle
Volume10
Issue number11
DOIs
Publication statusPublished - Jun 1 2011

Fingerprint

Pseudoxanthoma Elasticum
Vitamin K 1
Vitamin K
Diet
Calcium
Disease Progression
Organic Anion Transporters
Vitamin K 2
Calcinosis
Vibrissae
Skin
Elastic Tissue
Blood Vessels
Pathology
Staining and Labeling
Mutation
Serum
Proteins
matrix Gla protein

Keywords

  • Abcc6
  • Mineralization
  • Mouse
  • Pseudoxanthoma elasticum
  • Vitamin K

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Brampton, C., Yamaguchi, Y., Vanakker, O., Van Laer, L., Chen, L. H., Thakore, M., ... Saux, O. L. (2011). Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum. Cell Cycle, 10(11), 1810-1820. https://doi.org/10.4161/cc.10.11.15681

Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum. / Brampton, Christopher; Yamaguchi, Yukiko; Vanakker, Olivier; Van Laer, Lut; Chen, Li Hsieh; Thakore, Manoj; De Paepe, Anne; Pomozi, Viola; Szabó, P.; Martin, Ludovic; Váradi, A.; Saux, Olivier Le.

In: Cell Cycle, Vol. 10, No. 11, 01.06.2011, p. 1810-1820.

Research output: Contribution to journalArticle

Brampton, C, Yamaguchi, Y, Vanakker, O, Van Laer, L, Chen, LH, Thakore, M, De Paepe, A, Pomozi, V, Szabó, P, Martin, L, Váradi, A & Saux, OL 2011, 'Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum', Cell Cycle, vol. 10, no. 11, pp. 1810-1820. https://doi.org/10.4161/cc.10.11.15681
Brampton C, Yamaguchi Y, Vanakker O, Van Laer L, Chen LH, Thakore M et al. Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum. Cell Cycle. 2011 Jun 1;10(11):1810-1820. https://doi.org/10.4161/cc.10.11.15681
Brampton, Christopher ; Yamaguchi, Yukiko ; Vanakker, Olivier ; Van Laer, Lut ; Chen, Li Hsieh ; Thakore, Manoj ; De Paepe, Anne ; Pomozi, Viola ; Szabó, P. ; Martin, Ludovic ; Váradi, A. ; Saux, Olivier Le. / Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum. In: Cell Cycle. 2011 ; Vol. 10, No. 11. pp. 1810-1820.
@article{39d46f87af22422187c3cb6f18ae7e07,
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.",
keywords = "Abcc6, Mineralization, Mouse, Pseudoxanthoma elasticum, Vitamin K",
author = "Christopher Brampton and Yukiko Yamaguchi and Olivier Vanakker and {Van Laer}, Lut and Chen, {Li Hsieh} and Manoj Thakore and {De Paepe}, Anne and Viola Pomozi and P. Szab{\'o} and Ludovic Martin and A. V{\'a}radi and Saux, {Olivier Le}",
year = "2011",
month = "6",
day = "1",
doi = "10.4161/cc.10.11.15681",
language = "English",
volume = "10",
pages = "1810--1820",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "11",

}

TY - JOUR

T1 - Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum

AU - Brampton, Christopher

AU - Yamaguchi, Yukiko

AU - Vanakker, Olivier

AU - Van Laer, Lut

AU - Chen, Li Hsieh

AU - Thakore, Manoj

AU - De Paepe, Anne

AU - Pomozi, Viola

AU - Szabó, P.

AU - Martin, Ludovic

AU - Váradi, A.

AU - Saux, Olivier Le

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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.

AB - 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.

KW - Abcc6

KW - Mineralization

KW - Mouse

KW - Pseudoxanthoma elasticum

KW - Vitamin K

UR - http://www.scopus.com/inward/record.url?scp=79957919035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957919035&partnerID=8YFLogxK

U2 - 10.4161/cc.10.11.15681

DO - 10.4161/cc.10.11.15681

M3 - Article

VL - 10

SP - 1810

EP - 1820

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 11

ER -