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Increased calcium uptake and improved trabecular bone properties in intestinal alkaline phosphatase knockout mice

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Abstract

Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase (IAP) activity and calcium (Ca) absorption in the gut, as IAP acts as a protective mechanism inhibiting high Ca entry into enterocytes, preventing Ca overload. Here we evaluated Ca absorption and bone properties in knockout mice (KO) completely devoid of duodenal IAP (Akp3 −/− mice). Female C57BL/6 control mice (WT, n = 7) and KO mice (n = 10) were used to determine Ca absorption in vivo and by in situ isolated duodenal loops followed by histomorphometric analysis of duodenal villi and crypts. Bone mineral density, morphometry, histomorphometry and trabecular connectivity and biomechanical properties were measured on bones. We observed mild atrophy of the villi with lower absorption surface and a significantly higher Ca uptake in KO mice. While no changes were seen in cortical bone, we found better trabecular connectivity and biomechanical properties in the femurs of KO mice compared to WT mice. Our data indicate that IAP KO mice display higher intestinal Ca uptake, which over time appears to correlate with a positive effect on the biomechanical properties of trabecular bone.

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Acknowledgements

We thank Candela Retamozo, Damián Lescano and Alexia Cornejo for the technical assistance. This work was funded by Grant from CONICET (PIP 112 201501 00619 CO).

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Authors and Affiliations

  1. Bone Biology Laboratory, Cátedra de Química Biológica, Facultad de Ciencias Médicas, School of Medicine, Rosario National University, Santa Fe 3100, 2000, Rosario, Argentina

    Lucas R. Brun, M. Lombarte & A. Rigalli

  2. National Council of Scientific and Technical Research (CONICET), Rosario, Argentina

    Lucas R. Brun, M. Lombarte & A. Rigalli

  3. Histology and Embryology Department, School of Medicine, Rosario National University, Rosario, Argentina

    S. Roma & F. Perez

  4. Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA

    J. L. Millán

  5. Rosario National University Research Council, Rosario, Argentina

    A. Rigalli

Authors
  1. Lucas R. Brun
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  2. M. Lombarte
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  3. S. Roma
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  4. F. Perez
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  5. J. L. Millán
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  6. A. Rigalli
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Correspondence to Lucas R. Brun.

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Brun, L.R., Lombarte, M., Roma, S. et al. Increased calcium uptake and improved trabecular bone properties in intestinal alkaline phosphatase knockout mice. J Bone Miner Metab 36, 661–667 (2018). https://doi.org/10.1007/s00774-017-0887-7

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  • DOI: https://doi.org/10.1007/s00774-017-0887-7

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