Matrix gla protein and alkaline phosphatase are differently modulated in human dermal fibroblasts from PXE patients and controls

J Invest Dermatol. 2013 Apr;133(4):946-54. doi: 10.1038/jid.2012.460. Epub 2012 Dec 6.


Mineralization of elastic fibers in pseudoxanthoma elasticum (PXE) has been associated with low levels of carboxylated matrix gla protein (MGP), most likely as a consequence of reduced vitamin K (vit K) availability. Unexpectedly, vit K supplementation does not exert beneficial effects on soft connective tissue mineralization in the PXE animal model. To understand the effects of vit K supplementation and in the attempt to interfere with pathways leading to the accumulation of calcium and phosphate within PXE-mineralized soft connective tissues, we have conducted in vitro studies on dermal fibroblasts isolated from control subjects and from PXE patients. Cells were cultured in standard conditions and in calcifying medium (CM) in the presence of vit K1 and K2, or levamisole, an alkaline phosphatase (ALP) inhibitor. Control and PXE fibroblasts were characterized by a similar dose-dependent uptake of both vit K1 and vit K2, thus promoting a significant increase of total protein carboxylation in all cell lines. Nevertheless, MGP carboxylation remained much less in PXE fibroblasts. Interestingly, PXE fibroblasts exhibited a significantly higher ALP activity. Consistently, the mineralization process induced in vitro by a long-term culture in CM appeared unaffected by vit K, whereas it was abolished by levamisole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adult
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism*
  • Antifibrinolytic Agents / pharmacokinetics
  • Antifibrinolytic Agents / pharmacology
  • Calcification, Physiologic / drug effects
  • Calcification, Physiologic / physiology
  • Calcinosis / drug therapy
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Calcium / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Dermis / cytology
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / pathology
  • Humans
  • Levamisole / pharmacology
  • Middle Aged
  • Phosphates / metabolism
  • Pseudoxanthoma Elasticum / drug therapy*
  • Pseudoxanthoma Elasticum / metabolism*
  • Pseudoxanthoma Elasticum / pathology
  • Vitamin K / pharmacokinetics
  • Vitamin K / pharmacology*


  • Adjuvants, Immunologic
  • Antifibrinolytic Agents
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Phosphates
  • matrix Gla protein
  • Vitamin K
  • Levamisole
  • Alkaline Phosphatase
  • Calcium