Dual Effects of Bisphosphonates on Ectopic Skin and Vascular Soft Tissue Mineralization versus Bone Microarchitecture in a Mouse Model of Generalized Arterial Calcification of Infancy

The Journal of Investigative Dermatology
Qiaoli LiJouni Uitto

Abstract

Generalized arterial calcification of infancy is an intractable ectopic mineralization disorder caused by mutations in the ENPP1 gene, resulting in reduced plasma inorganic pyrophosphate (PPi) levels. We previously characterized the Enpp1(asj) mutant mouse as a model of generalized arterial calcification of infancy, and we have now explored the potential efficacy of bisphosphonates, nonhydrolyzable PPi analogs, in preventing ectopic mineralization in these mice. The mice were maintained on either basic diet (control) or diets containing etidronate or alendronate in three different concentrations (experimental). Considering low bioavailability of bisphosphonates when administered orally, subsequent studies tested the mice with subcutaneous injections of etidronate. The treatments were initiated at 4 weeks of age, and the degree of mineralization was assessed at 12 weeks of age by quantitation of calcium deposits in the muzzle skin containing dermal sheath of vibrissae and in aorta. We found that bisphosphonate treatments significantly reduced mineralization in skin and aorta. These changes in treated mice were accompanied with restoration of their bone microarchitecture, determined by microcomputed tomography. The inhibitory cap...Continue Reading

Citations

Dec 6, 2017·Molecular Medicine Reports·Hiu-Gwen TsangVicky E Macrae
Apr 13, 2018·Scientific Reports·Carolin BauerZouhair Aherrahrou
Sep 6, 2018·Nature Reviews. Endocrinology·Natasha M Appelman-Dijkstra, Socrates E Papapoulos
May 11, 2017·Orphanet Journal of Rare Diseases·Dominique P Germain
Mar 17, 2020·Journal of Biomedical Materials Research. Part a·Irina Y ZhuravlevaAlexander V Bogachev-Prokophiev
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Almudena Veiga-LopezFlora Szeri
Feb 13, 2021·Cardiovascular Research·Magnus Bäck, Jean-Baptiste Michel

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