---
_id: '12984'
abstract:
- lang: eng
  text: "Background\r\nPseudoxanthoma elasticum (PXE) is a rare hereditary disorder
    characterized by late onset and progressive calcification of elastic fibers in
    skin, eyes and the cardiovascular system, exemplifying a model for conditions
    characterized by soft tissue calcification.\r\nObjective\r\nThe aim of our study
    was to characterize cellular inorganic pyrophosphate (PPi) homeostasis in PXE.\r\nMethods\r\nGene
    expression of PPi metabolizing enzymes was determined by quantitative real-time
    PCR after incubation up to 21 days with or without addition of Na2HPO4. Extracellular
    and cytosolic PPi concentrations were measured by enzyme-linked bioluminescence
    assay. ALP and ENPP1 activity was determined spectrophotometrically. We further
    established a human cell culture model suitable for investigating PXE and related
    disorders without addition of artificial calcification triggers.\r\nResults\r\nIndependently
    of the experimental conditions, PXE fibroblasts revealed a higher degree of matrix
    calcification. We observed that matrix calcification was associated with altered
    gene expression of PPi metabolizing enzymes in PXE fibroblasts. In this context,
    PXE fibroblasts exhibited significantly higher expression of ALP and OPN and reduced
    mRNA expression and activity of ENPP1. Here, for the first time cytosolic and
    extracellular PPi levels were shown to be strongly reduced in PXE fibroblasts.
    We further showed that PPi concentration in bovine and human sera additives had
    a strong impact on matrix calcification. In a last experimental line, we demonstrated
    that addition of PPi analogs reduced matrix calcification of PXE fibroblasts most
    likely by reducing ALP and OPN mRNA expression, restoring ENPP1 activity and subsequently
    elevating PPi concentrations.\r\nConclusion\r\nThe results of our study along
    with recent findings point to the essential role of PPi as the central regulatory
    metabolites preventing matrix calcification in PXE. But what remains to be determined
    is the underlying molecular mechanism leading to depletion of PPi in PXE. We further
    suggest that supplementation of PPi analogs might counteract pathological calcification
    in PXE and related disorders."
author:
- first_name: Mareike
  full_name: Dabisch-Ruthe, Mareike
  id: '66516'
  last_name: Dabisch-Ruthe
  orcid: https://orcid.org/0009-0008-7644-0826
- first_name: Patricia
  full_name: Kuzaj, Patricia
  last_name: Kuzaj
- first_name: Christian
  full_name: Götting, Christian
  last_name: Götting
- first_name: Cornelius
  full_name: Knabbe, Cornelius
  last_name: Knabbe
- first_name: Doris
  full_name: Hendig, Doris
  last_name: Hendig
citation:
  ama: Dabisch-Ruthe M, Kuzaj P, Götting C, Knabbe C, Hendig D. Pyrophosphates as
    a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. <i>Journal
    of Dermatological Science</i>. 2014;75(2):109-120. doi:<a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">10.1016/j.jdermsci.2014.04.015</a>
  apa: Dabisch-Ruthe, M., Kuzaj, P., Götting, C., Knabbe, C., &#38; Hendig, D. (2014).
    Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma
    elasticum. <i>Journal of Dermatological Science</i>, <i>75</i>(2), 109–120. <a
    href="https://doi.org/10.1016/j.jdermsci.2014.04.015">https://doi.org/10.1016/j.jdermsci.2014.04.015</a>
  bjps: <b>Dabisch-Ruthe M <i>et al.</i></b> (2014) Pyrophosphates as a Major Inhibitor
    of Matrix Calcification in Pseudoxanthoma Elasticum. <i>Journal of Dermatological
    Science</i> <b>75</b>, 109–120.
  chicago: 'Dabisch-Ruthe, Mareike, Patricia Kuzaj, Christian Götting, Cornelius Knabbe,
    and Doris Hendig. “Pyrophosphates as a Major Inhibitor of Matrix Calcification
    in Pseudoxanthoma Elasticum.” <i>Journal of Dermatological Science</i> 75, no.
    2 (2014): 109–20. <a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">https://doi.org/10.1016/j.jdermsci.2014.04.015</a>.'
  chicago-de: 'Dabisch-Ruthe, Mareike, Patricia Kuzaj, Christian Götting, Cornelius
    Knabbe und Doris Hendig. 2014. Pyrophosphates as a major inhibitor of matrix calcification
    in Pseudoxanthoma elasticum. <i>Journal of Dermatological Science</i> 75, Nr.
    2: 109–120. doi:<a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">10.1016/j.jdermsci.2014.04.015</a>,
    .'
  din1505-2-1: '<span style="font-variant:small-caps;">Dabisch-Ruthe, Mareike</span>
    ; <span style="font-variant:small-caps;">Kuzaj, Patricia</span> ; <span style="font-variant:small-caps;">Götting,
    Christian</span> ; <span style="font-variant:small-caps;">Knabbe, Cornelius</span>
    ; <span style="font-variant:small-caps;">Hendig, Doris</span>: Pyrophosphates
    as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. In:
    <i>Journal of Dermatological Science</i> Bd. 75. Amsterdam, Elsevier  (2014),
    Nr. 2, S. 109–120'
  havard: M. Dabisch-Ruthe, P. Kuzaj, C. Götting, C. Knabbe, D. Hendig, Pyrophosphates
    as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum, Journal
    of Dermatological Science. 75 (2014) 109–120.
  ieee: 'M. Dabisch-Ruthe, P. Kuzaj, C. Götting, C. Knabbe, and D. Hendig, “Pyrophosphates
    as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum,” <i>Journal
    of Dermatological Science</i>, vol. 75, no. 2, pp. 109–120, 2014, doi: <a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">10.1016/j.jdermsci.2014.04.015</a>.'
  mla: Dabisch-Ruthe, Mareike, et al. “Pyrophosphates as a Major Inhibitor of Matrix
    Calcification in Pseudoxanthoma Elasticum.” <i>Journal of Dermatological Science</i>,
    vol. 75, no. 2, 2014, pp. 109–20, <a href="https://doi.org/10.1016/j.jdermsci.2014.04.015">https://doi.org/10.1016/j.jdermsci.2014.04.015</a>.
  short: M. Dabisch-Ruthe, P. Kuzaj, C. Götting, C. Knabbe, D. Hendig, Journal of
    Dermatological Science 75 (2014) 109–120.
  ufg: '<b>Dabisch-Ruthe, Mareike u. a.</b>: Pyrophosphates as a major inhibitor of
    matrix calcification in Pseudoxanthoma elasticum, in: <i>Journal of Dermatological
    Science</i> 75 (2014), H. 2,  S. 109–120.'
  van: Dabisch-Ruthe M, Kuzaj P, Götting C, Knabbe C, Hendig D. Pyrophosphates as
    a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. Journal
    of Dermatological Science. 2014;75(2):109–20.
date_created: 2025-06-17T06:52:59Z
date_updated: 2025-06-17T13:48:41Z
department:
- _id: DEP4010
doi: 10.1016/j.jdermsci.2014.04.015
intvolume: '        75'
issue: '2'
keyword:
- Pseudoxanthoma elasticum
- Calcification
- Pyrophosphate
- Bisphosphonate
- ABCC6
- Tissue nonspecific alkaline phosphate
- Ectonucleotide pyrophosphatase 1
language:
- iso: eng
page: 109-120
place: Amsterdam
publication: Journal of Dermatological Science
publication_identifier:
  eissn:
  - 1873-569X
  issn:
  - 0923-1811
publication_status: published
publisher: 'Elsevier '
quality_controlled: '1'
status: public
title: Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma
  elasticum
type: scientific_journal_article
user_id: '83781'
volume: 75
year: '2014'
...