Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum
- Author
- Christopher Brampton, Yukiko Yamaguchi, Olivier Vanakker (UGent) , Lut Van Laer (UGent) , Li-Hsieh Chen, Manoj Thakore, Anne De Paepe (UGent) , Viola Pomozi, Pal T Szabo, Ludovic Martin, Andras Varadi and Olivier Le Saux
- Organization
- 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
- ABC TRANSPORTER, MATRIX-GLA-PROTEIN, mineralization, Abcc6, mouse, vitamin K, pseudoxanthoma elasticum, MUTATIONS, MOLECULAR-GENETICS, CONNECTIVE TISSUES, CALCIFICATION, PHYLLOQUINONE, RATS, CARBOXYLATION, MRP6
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-1860429
- MLA
- Brampton, Christopher, et al. “Vitamin K Does Not Prevent Soft Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum.” CELL CYCLE, vol. 10, no. 11, 2011, pp. 1810–20, doi:10.4161/cc.10.11.15681.
- APA
- Brampton, C., Yamaguchi, Y., Vanakker, O., Van Laer, L., Chen, L.-H., Thakore, M., … Le Saux, O. (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
- Chicago author-date
- Brampton, Christopher, Yukiko Yamaguchi, Olivier Vanakker, Lut Van Laer, Li-Hsieh Chen, Manoj Thakore, Anne De Paepe, et al. 2011. “Vitamin K Does Not Prevent Soft Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum.” CELL CYCLE 10 (11): 1810–20. https://doi.org/10.4161/cc.10.11.15681.
- Chicago author-date (all authors)
- Brampton, Christopher, Yukiko Yamaguchi, Olivier Vanakker, Lut Van Laer, Li-Hsieh Chen, Manoj Thakore, Anne De Paepe, Viola Pomozi, Pal T Szabo, Ludovic Martin, Andras Varadi, and Olivier Le Saux. 2011. “Vitamin K Does Not Prevent Soft Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum.” CELL CYCLE 10 (11): 1810–1820. doi:10.4161/cc.10.11.15681.
- Vancouver
- 1.Brampton C, Yamaguchi Y, Vanakker O, Van Laer L, Chen L-H, Thakore M, et al. Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum. CELL CYCLE. 2011;10(11):1810–20.
- IEEE
- [1]C. Brampton et al., “Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum,” CELL CYCLE, vol. 10, no. 11, pp. 1810–1820, 2011.
@article{1860429, 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.}}, author = {{Brampton, Christopher and Yamaguchi, Yukiko and Vanakker, Olivier and Van Laer, Lut and Chen, Li-Hsieh and Thakore, Manoj and De Paepe, Anne and Pomozi, Viola and Szabo, Pal T and Martin, Ludovic and Varadi, Andras and Le Saux, Olivier}}, issn = {{1538-4101}}, journal = {{CELL CYCLE}}, keywords = {{ABC TRANSPORTER,MATRIX-GLA-PROTEIN,mineralization,Abcc6,mouse,vitamin K,pseudoxanthoma elasticum,MUTATIONS,MOLECULAR-GENETICS,CONNECTIVE TISSUES,CALCIFICATION,PHYLLOQUINONE,RATS,CARBOXYLATION,MRP6}}, language = {{eng}}, number = {{11}}, pages = {{1810--1820}}, title = {{Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum}}, url = {{http://doi.org/10.4161/cc.10.11.15681}}, volume = {{10}}, year = {{2011}}, }
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