Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum

• Published in: Journal of dermatological science Vol. 75; no. 2; pp. 109 - 120
• Main Authors: Dabisch-Ruthe, Mareike, Kuzaj, Patricia, Götting, Christian, Knabbe, Cornelius, Hendig, Doris
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01.08.2014
• Subjects: ABCC6; Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Bisphosphonate; Calcification; Calcinosis - genetics; Calcinosis - metabolism; Calcinosis - pathology; Case-Control Studies; Cells, Cultured; Dermatology; Diphosphates - metabolism; Ectonucleotide pyrophosphatase 1; Elastic Tissue - metabolism; Elastic Tissue - pathology; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation; Humans; Multidrug Resistance-Associated Proteins - genetics; Multidrug Resistance-Associated Proteins - metabolism; Osteopontin - genetics; Osteopontin - metabolism; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Pseudoxanthoma elasticum; Pseudoxanthoma Elasticum - genetics; Pseudoxanthoma Elasticum - metabolism; Pseudoxanthoma Elasticum - pathology; Pyrophosphatases - genetics; Pyrophosphatases - metabolism; Pyrophosphate; RNA, Messenger - metabolism; Signal Transduction; Time Factors; Tissue nonspecific alkaline phosphate; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Ectonucleotide pyrophosphatase 1; GGPP; ALP; FPP; OPN; BP; Geranylgeranylpyrophosphate; Tissue nonspecific alkaline phosphate; NHDF; Zoledronic acid; ENPP1; Inorganic pyrophosphate; Non-tissue specific alkaline phosphate; Bisphosphonate; ABCC6; ATP-binding cassette subfamily C member 6; Ectonucleotide pyrophospatase 1; Osteopontin; PP i; Polymerase chain reaction; Farnesylpyrophosphate; ZOL; Pyrophosphate; Calcification; Pseudoxanthoma elasticum; PXE; PCR; Normal human dermal fibroblast; PPi
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2014.04.015

Highlights • Strongly diminished pyrophosphate levels leading to intensified calcification of ECM in PXE cells. • We demonstrated a dysfunction of pyrophosphate generation in PXE fibroblasts. • An association of ABCC6 in cellular pyrophosphate homeostasis was shown. • Bisphosphonates (pyrophosphate analogs) as promising drug to inhibit pathological calcification in PXE.