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Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption

Osteoclasts are bone‐resorbing cells that play an essential role in maintaining bone homeostasis. Zinc (Zn) has been reported to inhibit osteoclast‐mediated bone resorption, but the mechanism of this action has not been clarified. Zn homeostasis is tightly controlled by the coordinated actions of ma...

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Autores principales: Sasaki, Sun, Tsukamoto, Manami, Saito, Masaki, Hojyo, Shintaro, Fukada, Toshiyuki, Takami, Masamichi, Furuichi, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881542/
https://www.ncbi.nlm.nih.gov/pubmed/29632817
http://dx.doi.org/10.1002/2211-5463.12399
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author Sasaki, Sun
Tsukamoto, Manami
Saito, Masaki
Hojyo, Shintaro
Fukada, Toshiyuki
Takami, Masamichi
Furuichi, Tatsuya
author_facet Sasaki, Sun
Tsukamoto, Manami
Saito, Masaki
Hojyo, Shintaro
Fukada, Toshiyuki
Takami, Masamichi
Furuichi, Tatsuya
author_sort Sasaki, Sun
collection PubMed
description Osteoclasts are bone‐resorbing cells that play an essential role in maintaining bone homeostasis. Zinc (Zn) has been reported to inhibit osteoclast‐mediated bone resorption, but the mechanism of this action has not been clarified. Zn homeostasis is tightly controlled by the coordinated actions of many Zn transporters. The Zn transporter ZIP14/Slc39a14 is involved in various physiological functions; hence, Zip14‐knockout (KO) mice exhibit multiple phenotypes. In this study, we thoroughly investigated the bone phenotypes of Zip14‐KO mice, demonstrating that the KO mice exhibited osteopenia in both trabecular and cortical bones. In Zip14‐KO mice, bone resorption was increased, whereas the bone formation rate was unchanged. Zip14 mRNA was expressed in normal osteoclasts both in vivo and in vitro, but receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis was not impaired in bone marrow‐derived macrophages prepared from Zip14‐KO mice. These results suggest that ZIP14 regulates bone homeostasis by inhibiting bore resorption and that in Zip14‐KO mice, bone resorption is increased due to the elimination of this inhibitory regulation. Further studies are necessary to conclude whether the enhancement of bone resorption in Zip14‐KO mice is due to a cell‐autonomous or a non‐cell‐autonomous osteoclast defect.
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spelling pubmed-58815422018-04-09 Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption Sasaki, Sun Tsukamoto, Manami Saito, Masaki Hojyo, Shintaro Fukada, Toshiyuki Takami, Masamichi Furuichi, Tatsuya FEBS Open Bio Research Articles Osteoclasts are bone‐resorbing cells that play an essential role in maintaining bone homeostasis. Zinc (Zn) has been reported to inhibit osteoclast‐mediated bone resorption, but the mechanism of this action has not been clarified. Zn homeostasis is tightly controlled by the coordinated actions of many Zn transporters. The Zn transporter ZIP14/Slc39a14 is involved in various physiological functions; hence, Zip14‐knockout (KO) mice exhibit multiple phenotypes. In this study, we thoroughly investigated the bone phenotypes of Zip14‐KO mice, demonstrating that the KO mice exhibited osteopenia in both trabecular and cortical bones. In Zip14‐KO mice, bone resorption was increased, whereas the bone formation rate was unchanged. Zip14 mRNA was expressed in normal osteoclasts both in vivo and in vitro, but receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis was not impaired in bone marrow‐derived macrophages prepared from Zip14‐KO mice. These results suggest that ZIP14 regulates bone homeostasis by inhibiting bore resorption and that in Zip14‐KO mice, bone resorption is increased due to the elimination of this inhibitory regulation. Further studies are necessary to conclude whether the enhancement of bone resorption in Zip14‐KO mice is due to a cell‐autonomous or a non‐cell‐autonomous osteoclast defect. John Wiley and Sons Inc. 2018-02-26 /pmc/articles/PMC5881542/ /pubmed/29632817 http://dx.doi.org/10.1002/2211-5463.12399 Text en © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Sasaki, Sun
Tsukamoto, Manami
Saito, Masaki
Hojyo, Shintaro
Fukada, Toshiyuki
Takami, Masamichi
Furuichi, Tatsuya
Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption
title Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption
title_full Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption
title_fullStr Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption
title_full_unstemmed Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption
title_short Disruption of the mouse Slc39a14 gene encoding zinc transporter ZIP14 is associated with decreased bone mass, likely caused by enhanced bone resorption
title_sort disruption of the mouse slc39a14 gene encoding zinc transporter zip14 is associated with decreased bone mass, likely caused by enhanced bone resorption
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881542/
https://www.ncbi.nlm.nih.gov/pubmed/29632817
http://dx.doi.org/10.1002/2211-5463.12399
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