Progressive calcification of elastic fibers is typical of Pseudoxanthoma elasticum (PXE), a rare genetic disease due to mutations in the ABCC6 gene.The pathogenesis of mineral- ization is only partially known.1 Previous studies on dermal fibroblasts from PXE patients demonstrated that the calcifica- tion process is associated to impaired carboxylation of matrix- gla-protein that, in its active form, binds to calcium, therefore inhibiting mineralization.2 However, the recent observation that PXE fibroblasts exhibit also a significant upregulation of alka- line phosphatase (TNAP) activity suggested that an abnormal phosphate metabolism may take place within soft connective tis- sues, thus contributing to ectopic calcification.3 To improve the understanding of PXE it was developed a transgenic mouse model by specifically inactivating the Abcc6 gene.4 Consistently, Abcc6-/- mice recapitulate several histopathological findings typ- ical of PXE, including the slow progression of the disease.5 Aim of the present study was to isolate fibroblasts from Abcc6+/+ and Abcc6-/- mice of different ages (i.e. before and after the devel- opment of ectopic calcification) and to investigate proteins con- trolling phosphate levels in the extracellular matrix. Results demonstrate a down-regulation of pyrophosphatase/phosphodi- esterase 1, of progressive ankylosis protein and of osteopontin, whereas bone morphogenetic protein 2 and TNAP activity were up-regulated in fibroblasts from Abcc6-/- animals. These data support the hypothesis that in PXE the unbalanced ratio between factors locally controlling both calcium and phosphate homeostasis are crucial in triggering tissue calcification.
|Data di pubblicazione:||2013|
|Titolo:||DIFFERENTIALLY EXPRESSED PROTEINS IN FIBROBLASTS FROM Abcc6-/- AND Abcc6+/+ MICE HIGHLIGHT THE ROLE OF A LOCALLY ALTERED PHOSPHATE METABOLISM IN THE OCCURRENCE OF ECTOPIC CALCIFICATION|
|Autori:||Bartolomeo, A.; Boraldi, F.; Uitto, J.; Quaglino, D.|
|Nome del convegno:||XXXIII Riunione Nazionale SISC|
|Luogo del convegno:||Pavia|
|Data del convegno:||3-4 October|
|Titolo del libro:||PROCEEDINGS OF THE XXXIII NATIONAL MEETING OF THE ITALIAN SOCIETY FOR THE STUDY OF CONNECTIVE TISSUES (SISC)|
|Appare nelle tipologie:||Abstract in Rivista|
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