Alkaline Phosphatase and Hypophosphatasia
TLDR
Enzyme replacement using mineral-targeted TNAP from birth prevented severe HPP in TNAP-knockout mice and was then shown to rescue and substantially treat infants and young children with life-threatening HPP.Abstract:
Hypophosphatasia (HPP) results from ALPL mutations leading to deficient activity of the tissue-non-specific alkaline phosphatase isozyme (TNAP) and thereby extracellular accumulation of inorganic pyrophosphate (PPi), a natural substrate of TNAP and potent inhibitor of mineralization. Thus, HPP features rickets or osteomalacia and hypomineralization of teeth. Enzyme replacement using mineral-targeted TNAP from birth prevented severe HPP in TNAP-knockout mice and was then shown to rescue and substantially treat infants and young children with life-threatening HPP. Clinical trials are revealing aspects of HPP pathophysiology not yet fully understood, such as craniosynostosis and muscle weakness when HPP is severe. New treatment approaches are under development to improve patient care.read more
Citations
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Journal ArticleDOI
Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment.
TL;DR: Paediatric hypophosphatasia was the last type of rickets or osteomalacia to await a medical treatment and significant successes for severely affected paediatric patients are recognized using asfotase alfa, a bone-targeted recombinant TNSALP.
Journal ArticleDOI
Alkaline phosphatase: Structure, expression and its function in bone mineralization.
TL;DR: The increased level of ALP expression and development in this environment would undoubtedly provide new and essential information about the fundamental molecular mechanisms of bone formation, offer therapeutic possibilities for the management of bone-related diseases.
Journal ArticleDOI
Hypophosphatasia: An overview For 2017.
TL;DR: Significant successes using asfotase alfa, a mineral-targeted recombinant TNSALP, are published concerning severely affected newborns, infants, and children.
Journal ArticleDOI
Noble Metal Nanoparticle-Based Multicolor Immunoassays: An Approach toward Visual Quantification of the Analytes with the Naked Eye.
TL;DR: This work reviews the state of the art in noble metal nanoparticle-based multicolor colorimetric strategies adopted for visual quantification by the naked eye and proposes the future development of next-generationMulticolor qualification strategies.
Journal ArticleDOI
Matrix vesicles from chondrocytes and osteoblasts: Their biogenesis, properties, functions and biomimetic models
Massimo Bottini,Saida Mebarek,Karen L. Anderson,Agnieszka Strzelecka-Kiliszek,Lukasz Bozycki,Ana Maria Simao,Maytê Bolean,Pietro Ciancaglini,Joanna Bandorowicz Pikula,Slawomir Pikula,David Magne,Niels Volkmann,Dorit Hanein,José Luis Millán,René Buchet +14 more
TL;DR: The prospects of employing upcoming experimental models to deepen the understanding of MV-mediated mineralization and mineralization disorders such as the use of reconstituted lipid vesicles, proteoliposomes and, native sample preparations and high-resolution technologies are discussed.
References
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Journal ArticleDOI
Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization
Lovisa Hessle,Kristen Johnson,H. Clarke Anderson,Sonoko Narisawa,Adnan Sali,James W. Goding,Robert Terkeltaub,José Luis Millán +7 more
TL;DR: The results suggest that inhibiting PC-1 function may be a viable therapeutic strategy for hypophosphatasia, and interfere with TNAP activity may correct pathological hyperossification because of PPi insufficiency.
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The Possible Significance of Hexosephosphoric Esters in Ossification.
TL;DR: Robison was able to study for two years in Leipzig in the kdbordtories of Professor Hantz as mentioned in this paper, where he obtained a scholarship to attend the University of Nottingham.
Journal ArticleDOI
Isolation and characterization of calcifying matrix vesicles from epiphyseal cartilage.
TL;DR: The matrix vesicles possess enzymes that can increase the local concentration of orthophosphate and thus could lead to the formation of hydroxyapatite, and may also provide a mechanism for ATP-dependent transport of calcium or phosphate into the lumen of the vesicle with resultant mineralization.
Journal ArticleDOI
Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis.
Journal ArticleDOI
Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders.
Dympna Harmey,Lovisa Hessle,Sonoko Narisawa,Kristen Johnson,Robert Terkeltaub,José Luis Millán +5 more
TL;DR: In this article, the authors crossbred Akp2−/− mice to ank/ank mice and found a partial normalization of the mineralization phenotypes and PPi levels.
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