title: Administration of vitamin K does not counteract the ectopic mineralization of connective tissues in Abcc6 (-/-) mice, a model for pseudoxanthoma elasticum.
abstract: Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder manifesting with ectopic calcification of peripheral connective tissues, caused by mutations in the ABCC6 gene. Alterations in vitamin K metabolism have been suggested to contribute to the pathomechanisms of the mineralization process. In this study we administered vitamin K or its glutathione conjugate (K3-GSH) into Abcc6 (-/-) mice which recapitulate features of PXE. Oral administration of vitamin K2 in dosages, which vastly exceed the amounts in control diet or the recommended amounts for humans, did not alter the ectopic mineralization in Abcc6 (-/-) mice. Similarly, intravenous administration of K3-GSH did not alter the degree of mineralization. Testing of vitamin K2, K3 and K3-GSH in an in vitro calcification system provided no evidence of mineralization inhibition. Collectively, our data suggest that vitamin K deficiency in the peripheral tissues is not a simple explanation for development of mineral deposits in PXE.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Qiujie
authors.initials: Q
authors.lastname: Jiang
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Alix E
authors.initials: AE
authors.lastname: Grand-Pierre
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation; D011561:Pseudoxanthoma Elasticum / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014812:Vitamin K / Q000008:administration & dosage* / Q000378:metabolism; D014813:Vitamin K Deficiency
chemical_list: D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014812:Vitamin K; C504743:Abcc6 protein, mouse