Orientation of Mineral Crystallites and Mineral Density During Skeletal Development in Mice Deficient in Tissue Nonspecific Alkaline Phosphatase

Authors

  • W Tesch,

    1. Ludwig Boltzmann Institute of Osteology, 4th Medical Department, Hanusch Hospital and UKH Meidling, Vienna, Austria
    2. Erich Schmid Institute of Materials Science, Austrian Academy of Sciences and Institute of Metal Physics, University of Leoben, Leoben, Austria
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  • T Vandenbos,

    1. Department of Periodontology, Academic Center for Dentistry, Amsterdam, The Netherlands
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  • P Roschgr,

    1. Ludwig Boltzmann Institute of Osteology, 4th Medical Department, Hanusch Hospital and UKH Meidling, Vienna, Austria
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  • N Fratzl-Zelman,

    1. Ludwig Boltzmann Institute of Osteology, 4th Medical Department, Hanusch Hospital and UKH Meidling, Vienna, Austria
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  • K Klaushofer,

    1. Ludwig Boltzmann Institute of Osteology, 4th Medical Department, Hanusch Hospital and UKH Meidling, Vienna, Austria
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  • W Beertsen,

    1. Department of Periodontology, Academic Center for Dentistry, Amsterdam, The Netherlands
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  • P Fratzl PhD

    Corresponding author
    1. Erich Schmid Institute of Materials Science, Austrian Academy of Sciences and Institute of Metal Physics, University of Leoben, Leoben, Austria
    • Erich Schmid Institute of Materials Science, Austrian Academy of Sciences, Institute of Metal Physics, University of Leoben, Jahnstr. 12, A-8700 Leoben, Austria
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  • The authors have no conflict of interest

Abstract

Tissue nonspecific alkaline phosphatase (TNALP) is thought to play an important role in mineralization processes, although its exact working mechanism is not known. In the present investigation we have studied mineral crystal characteristics in the developing skeleton of TNALP-deficient mice. Null mutants (n = 7) and their wild-type littermates (n = 7) were bred and killed between 8 and 22 days after birth. Skeletal tissues were processed to assess mineral characteristics (small angle X-ray scattering, quantitative backscattered electron imaging), and to analyze bone by light microscopy and immunolabeling. The results showed a reduced longitudinal growth and a strongly delayed epiphyseal ossification in the null mutants. This was accompanied by disturbances in mineralization pattern, in that crystallites were not orderly aligned with respect to the longitudinal axis of the cortical bone. Among the null mutants, a great variability in the mineralization parameters was noticed. Also, immunolabeling of osteopontin (OPN) revealed an abnormal distribution pattern of the protein within the bone matrix. Whereas in the wild-type animals OPN was predominantly observed in cement and reversal lines, in the null mutants, OPN was also randomly dispersed throughout the nonmineralized matrix, with focal densities. In contrast, the distribution pattern of osteocalcin (OC) was comparable in both types of animals. It is concluded that ablation of TNALP results not only in hypomineralization of the skeleton, but also in a severe disorder of the mineral crystal alignment pattern in the corticalis of growing long bone in association with a disordered matrix architecture, presumably as a result of impaired bone remodeling and maturation.

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