Deciphering Ectopic Calcification: Contribution of the Rare, Inherited Disorder Pseudoxanthoma Elasticum - European Medical Journal

Deciphering Ectopic Calcification: Contribution of the Rare, Inherited Disorder Pseudoxanthoma Elasticum

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*Ivonne Pasquali Ronchetti

The author has declared no conflicts of interest.

EMJ Rheumatol. ;2[1]:89-97. DOI/10.33590/emjrheumatol/10312673.
Soft connective tissue calcification, ectopic calcification, extracellular matrix calcification, fibroblast gene expression, fibroblast epigenetic changes, calcification genetic disorders, pseudoxanthoma elasticum.

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Soft connective tissue calcification is still an intriguing problem due to the high number of genes, proteins, and enzymes involved in the process. Numerous epidemiological and experimental studies of the ectopic calcification associated with metabolic, inflammatory, and degenerative disorders have been performed. Moreover, in the last decade, great efforts have been made in studying the genetic disorders leading to soft connective tissue calcification, trying to understand the imbalance between pro and anti-calcifying factors in the different disorders, and why calcification occurs only in certain body regions (which often differ between the various genetic defects). The rare, inherited disorder pseudoxanthoma elasticum (PXE), which is caused by mutations in the ABCC6 gene, is an interesting model because the gene responsible is mainly expressed in the liver, whereas calcification affects peripheral soft connective tissues. It has been suggested that liver deficiency of the protein encoded by ABCC6 directly induces peripheral calcification, although, in contrast, several studies both in humans and in transgenic mice indicate that peripheral mesenchymal cells might be permanently involved in PXE calcification. In this review, the author suggests that early in development PXE cells may undergo epigenetic changes and acquire a permanent pro-calcific signature. However, given the complexity of the calcification process and the metabolic inter-exchanges among the different calcific genetic disorders, a bioinformatic approach analysing data ranging from genes to functional proteins and clinical features may complete the puzzle and provide new therapeutic perspectives in PXE, as well as in other calcific disorders.

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