1. Enzyme replacement for craniofacial skeletal defects and craniosynostosis in murine hypophosphatasia.

    Bone 78:203 (2015) PMID 25959417 PMCID PMC4466206

    Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl(-/-) mice exhibit many characteristics seen in infantile HP...
  2. Effects of etidronate on the Enpp1-/- mouse model of generalized arterial calcification of infancy.

    International Journal of Molecular Medicine 36(1):159 (2015) PMID 25975272 PMCID PMC4494596

    Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder of spontaneous infantile arterial and periarticular calcification which is attributed to mutations in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) gene. Whilst the bisphosphonate, etidronate...
  3. Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification.

    Journal of Bone and Mineral Research 30(5):824 (2015) PMID 25428889 PMCID PMC4406354

    Medial vascular calcification (MVC) is a pathological phenomenon that causes vascular stiffening and can lead to heart failure; it is common to a variety of conditions, including aging, chronic kidney disease, diabetes, obesity, and a variety of rare genetic diseases. These conditions share the ...
  4. An investigation of the mineral in ductile and brittle cortical mouse bone.

    Journal of Bone and Mineral Research 30(5):786 (2015) PMID 25418329 PMCID PMC4507744

    Bone is a strong and tough material composed of apatite mineral, organic matter, and water. Changes in composition and organization of these building blocks affect bone's mechanical integrity. Skeletal disorders often affect bone's mineral phase, either by variations in the collagen or directly ...
  5. Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl-/- mice by administration of soluble (non-targeted) chimeric alkaline phosphatase.

    Bone 72:137 (2015) PMID 25433339 PMCID PMC4283789

    Hypophosphatasia (HPP) results from ALPL gene mutations, which lead to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP, in the extracellular space. HPP cause...
  6. Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl(-/-) mice by administration of soluble (non-targeted) chimeric alkaline phosphatase.

    Bone 72:137 (2015) PMID 25433339

    Hypophosphatasia (HPP) results from ALPL gene mutations, which lead to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP, in the extracellular space. HPP cause...
  7. Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl(-/-) mice by administration of soluble (non-targeted) chimeric alkaline phosphatase.

    Bone 72:137 (2015) PMID 25433339 PMCID PMC4283789

    Hypophosphatasia (HPP) results from ALPL gene mutations, which lead to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP, in the extracellular space. HPP cause...
  8. Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl(-/-) mice by administration of soluble (non-targeted) chimeric alkaline phosphatase.

    Bone 72:137 (2015) PMID 25433339

    Hypophosphatasia (HPP) results from ALPL gene mutations, which lead to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP, in the extracellular space. HPP cause...
  9. Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl−/− mice by administration of soluble (non-targeted) chimeric alkaline phosphatase

    Bone 72:137 (2015) PMID 25433339 PMCID PMC4283789

    Hypophosphatasia (HPP) results from ALPL gene mutations, which lead to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP, in the extracellular space....
  10. Intestinal alkaline phosphatase deficiency leads to lipopolysaccharide desensitization and faster weight gain.

    Infection and Immunity 83(1):247 (2015) PMID 25348635 PMCID PMC4288875

    Animals develop in the presence of complex microbial communities, and early host responses to these microbes can influence key aspects of development, such as maturation of the immune system, in ways that impact adult physiology. We previously showed that the zebrafish intestinal alkaline phosph...
  11. Intestinal alkaline phosphatase deficiency leads to lipopolysaccharide desensitization and faster weight gain.

    Infection and Immunity 83(1):247 (2015) PMID 25348635

    Animals develop in the presence of complex microbial communities, and early host responses to these microbes can influence key aspects of development, such as maturation of the immune system, in ways that impact adult physiology. We previously showed that the zebrafish intestinal alkaline phosph...
  12. Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase.

    PLoS ONE 10(3):e0119874 (2015) PMID 25775211 PMCID PMC4361680

    The conserved active site of alkaline phosphatases (AP) contains catalytically important Zn2+ (M1 and M2) and Mg2+-sites (M3) and a fourth peripheral Ca2+ site (M4) of unknown significance. We have studied Ca2+ binding to M1-4 of tissue-nonspecific AP (TNAP), an enzyme crucial for skeletal miner...
  13. What Can We Learn About the Neural Functions of TNAP from Studies on Other Organs and Tissues?

    Sub-Cellular Biochemistry 76:155 (2015) PMID 26219711

    To-date, the function of tissue-nonspecific alkaline phosphatase (TNAP) has largely been defined through studies in patients and mice affected by hypophosphatasia (HPP), a rare inborn-error-of-metabolism caused by mutation(s) in the TNAP gene (ALPL). The skeletal disease in HPP can be explained ...
  14. Intestinal alkaline phosphatase deficiency leads to lipopolysaccharide desensitization and faster weight gain.

    Infection and Immunity 83(1):247 (2015) PMID 25348635 PMCID PMC4288875

    Animals develop in the presence of complex microbial communities, and early host responses to these microbes can influence key aspects of development, such as maturation of the immune system, in ways that impact adult physiology. We previously showed that the zebrafish intestinal alkaline phosph...
  15. Intestinal alkaline phosphatase deficiency leads to lipopolysaccharide desensitization and faster weight gain.

    Infection and Immunity 83(1):247 (2015) PMID 25348635 PMCID PMC4288875

    Animals develop in the presence of complex microbial communities, and early host responses to these microbes can influence key aspects of development, such as maturation of the immune system, in ways that impact adult physiology. We previously showed that the zebrafish intestinal alkaline phosph...
  16. Tissue-nonspecific Alkaline Phosphatase Regulates Purinergic Transmission in the Central Nervous System During Development and Disease.

    Computational and Structural Biotechnology Journal 13:95 (2015) PMID 25709758 PMCID PMC4334957

    Tissue-nonspecific alkaline phosphatase (TNAP) is one of the four isozymes in humans and mice that have the capacity to hydrolyze phosphate groups from a wide spectrum of physiological substrates. Among these, TNAP degrades substrates implicated in neurotransmission. Transgenic mice lacking TNAP...
  17. The critical role of membralin in postnatal motor neuron survival and disease.

    eLife 4 (2015) PMID 25977983 PMCID PMC4460860

    Hitherto, membralin has been a protein of unknown function. Here, we show that membralin mutant mice manifest a severe and early-onset motor neuron disease in an autosomal recessive manner, dying by postnatal day 5-6. Selective death of lower motor neurons, including those innervating the limbs,...
  18. Tissue-nonspecific Alkaline Phosphatase Regulates Purinergic Transmission in the Central Nervous System During Development and Disease.

    Computational and Structural Biotechnology Journal 13:95 (2015) PMID 25709758

    Tissue-nonspecific alkaline phosphatase (TNAP) is one of the four isozymes in humans and mice that have the capacity to hydrolyze phosphate groups from a wide spectrum of physiological substrates. Among these, TNAP degrades substrates implicated in neurotransmission. Transgenic mice lacking TNAP...
  19. Intestinal alkaline phosphatase deficiency leads to lipopolysaccharide desensitization and faster weight gain.

    Infection and Immunity 83(1):247 (2015) PMID 25348635 PMCID PMC4288875

    Animals develop in the presence of complex microbial communities, and early host responses to these microbes can influence key aspects of development, such as maturation of the immune system, in ways that impact adult physiology. We previously showed that the zebrafish intestinal alkaline phosph...
  20. Reference point indentation is not indicative of whole mouse bone measures of stress intensity fracture toughness.

    Bone 69:174 (2014) PMID 25280470 PMCID PMC4228060

    Bone fragility is a concern for aged and diseased bone. Measuring bone toughness and understanding fracture properties of the bone are critical for predicting fracture risk associated with age and disease and for preclinical testing of therapies. A reference point indentation technique (BioDent)...