Histomorphometry of ectopic mineralization using undecalcified frozen bone sections

2018 ◽  
Vol 81 (11) ◽  
pp. 1318-1324
Author(s):  
Ryuji Fujihara ◽  
Yoichi Chiba ◽  
Toshitaka Nakagawa ◽  
Ryuta Murakami ◽  
Koichi Matsumoto ◽  
...  
Keyword(s):  
Ectopic Mineralization ◽  
Frozen Bone

scholarly journals Disruption of Abcc6 Transporter in Zebrafish Causes Ocular Calcification and Cardiac Fibrosis

2020 ◽  
Vol 22 (1) ◽  
pp. 278
Author(s):  
Jianjian Sun ◽  
Peilu She ◽  
Xu Liu ◽  
Bangjun Gao ◽  
Daqin Jin ◽  
...  
Keyword(s):  
Vitamin K ◽  
Cardiac Fibrosis ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Matrix Gla Protein ◽  
Ectopic Calcification ◽  
Transcription Activator ◽  
Multisystem Disorder ◽  
Ectopic Mineralization ◽  
Extensive Calcification

Pseudoxanthoma elasticum (PXE), caused by ABCC6/MRP6 mutation, is a heritable multisystem disorder in humans. The progressive clinical manifestations of PXE are accompanied by ectopic mineralization in various connective tissues. However, the pathomechanisms underlying the PXE multisystem disorder remains obscure, and effective treatment is currently available. In this study, we generated zebrafish abcc6a mutants using the transcription activator-like effector nuclease (TALEN) technique. In young adult zebrafish, abcc6a is expressed in the eyes, heart, intestine, and other tissues. abcc6a mutants exhibit extensive calcification in the ocular sclera and Bruch’s membrane, recapitulating part of the PXE manifestations. Mutations in abcc6a upregulate extracellular matrix (ECM) genes, leading to fibrotic heart with reduced cardiomyocyte number. We found that abcc6a mutation reduced levels of both vitamin K and pyrophosphate (PPi) in the serum and diverse tissues. Vitamin K administration increased the gamma-glutamyl carboxylated form of matrix gla protein (cMGP), alleviating ectopic calcification and fibrosis in vertebrae, eyes, and hearts. Our findings contribute to a comprehensive understanding of PXE pathophysiology from zebrafish models.

scholarly journals Structural and Functional Characterization of the ABCC6 Transporter in Hepatic Cells: Role on PXE, Cancer Therapy and Drug Resistance

2021 ◽  
Vol 22 (6) ◽  
pp. 2858
Author(s):  
Faustino Bisaccia ◽  
Prashant Koshal ◽  
Vittorio Abruzzese ◽  
Maria Antonietta Castiglione Morelli ◽  
Angela Ostuni
Keyword(s):  
Cancer Therapy ◽  
Functional Characterization ◽  
Physiological Role ◽  
Pseudoxanthoma Elasticum ◽  
Connective Tissues ◽  
Functional Studies ◽  
Extracellular Milieu ◽  
Hepatic Cells ◽  
Ectopic Mineralization ◽  
Anti Cancer

Pseudoxanthoma elasticum (PXE) is a complex autosomal recessive disease caused by mutations of ABCC6 transporter and characterized by ectopic mineralization of soft connective tissues. Compared to the other ABC transporters, very few studies are available to explain the structural components and working of a full ABCC6 transporter, which may provide some idea about its physiological role in humans. Some studies suggest that mutations of ABCC6 in the liver lead to a decrease in some circulating factor and indicate that PXE is a metabolic disease. It has been reported that ABCC6 mediates the efflux of ATP, which is hydrolyzed in PPi and AMP; in the extracellular milieu, PPi gives potent anti-mineralization effect, whereas AMP is hydrolyzed to Pi and adenosine which affects some cellular properties by modulating the purinergic pathway. Structural and functional studies have demonstrated that silencing or inhibition of ABCC6 with probenecid changed the expression of several genes and proteins such as NT5E and TNAP, as well as Lamin, and CDK1, which are involved in cell motility and cell cycle. Furthermore, a change in cytoskeleton rearrangement and decreased motility of HepG2 cells makes ABCC6 a potential target for anti-cancer therapy. Collectively, these findings suggested that ABCC6 transporter performs functions that modify both the external and internal compartments of the cells.

scholarly journals Ectopic Mineralization in Fibroblast Cultures

1984 ◽  
Vol 47 (1) ◽  
pp. 43-55 ◽  
Author(s):  
Masayoshi KUMEGAWA ◽  
Masahiko HIRAMATSU ◽  
Toshihiko YAJIMA
Keyword(s):  
Fibroblast Cultures ◽  
Ectopic Mineralization

Mandible reconstruction and autogenous frozen bone graft: Experimental study on rats

Microsurgery ◽  
2001 ◽  
Vol 21 (4) ◽  
pp. 131-134 ◽  
Author(s):  
Cristina Garusi ◽  
Luca Calabrese ◽  
Gioacchino Giugliano ◽  
Giovanni Mazzarol ◽  
Stefano Podrecca ◽  
...  
Keyword(s):  
Experimental Study ◽  
Bone Graft ◽  
Mandible Reconstruction ◽  
Frozen Bone

scholarly journals Pseudoxanthoma Elasticum as a Paradigm of Heritable Ectopic Mineralization Disorders

2019 ◽  
Vol 189 (2) ◽  
pp. 216-225 ◽  
Author(s):  
Qiaoli Li ◽  
Koen van de Wetering ◽  
Jouni Uitto
Keyword(s):  
Pseudoxanthoma Elasticum ◽  
Ectopic Mineralization

scholarly journals Microvasculopathy, Luminal Calcification and Premature Aging in Fetuin-A Deficient Mice

2019 ◽  
Author(s):  
Marietta Herrmann ◽  
Anne Babler ◽  
Irina Moshkova ◽  
Felix Gremse ◽  
Fabian Kiessling ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Early Stage ◽  
Analytical Electron Microscopy ◽  
Premature Aging ◽  
Fetuin A ◽  
Genome Wide ◽  
Ectopic Mineralization ◽  
Brown Adipose ◽  
Calciprotein Particles ◽  
Deficient Mice

AbstractObjectiveThe plasma protein fetuin-A mediates the formation of protein-mineral colloids known as calciprotein particles (CPP) – rapid clearance of these CPP by the reticuloendothelial system prevents errant mineral precipitation and therefore ectopic mineralization (calcification). The mutant mouse strain D2,Ahsg-/- combines fetuin-A deficiency with the mineralization-prone DBA/2 genetic background, having a particularly severe compound phenotype of microvascular and soft tissue mineralization. Here we studied mechanisms leading to soft tissue mineralization, organ damage and premature aging in these mice.Approach and ResultsWe analyzed mice longitudinally by echocardiography, X-ray-computed tomography, analytical electron microscopy, histology, mass spectrometry proteomics, and genome-wide microarray-based expression analyses of D2 wildtype and Ahsg-/- mice.Fetuin-A deficient mice had calcified lesions in myocardium, lung, brown adipose tissue, reproductive organs, spleen, pancreas, kidney and the skin, associated with reduced growth, cardiac output and premature aging. Importantly, early stage calcified lesions presented in the lumen of the microvasculature suggesting precipitation of mineral containing complexes from the fluid phase of blood. Genome-wide expression analysis of calcified lesions and surrounding (not calcified) tissue, together with morphological observations, indicated that the ectopic mineralization was not associated with osteochondrogenic cell differentiation, but rather with thrombosis and fibrosis.ConclusionsCollectively, these results demonstrate that pathological mineralization can start by intravascular mineral deposition causing microvasculopathy, which impacts on growth, organ function and survival. Our study underscores the importance of fetuin-A and related systemic regulators of mineralized matrix metabolism to prevent cardiovascular disease, especially in dysregulated mineral homeostasis.

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