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Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice

Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C. In Hyp mice, a murine model for X-linked hypophosphatemia (XLH), Phex deficiency results in the overproduction of FGF23 in osteocytes, which leads to hypophosphatemia and impaired vitamin D metab...

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Autores principales: Miyagawa, Kazuaki, Yamazaki, Miwa, Kawai, Masanobu, Nishino, Jin, Koshimizu, Takao, Ohata, Yasuhisa, Tachikawa, Kanako, Mikuni-Takagaki, Yuko, Kogo, Mikihiko, Ozono, Keiichi, Michigami, Toshimi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977859/
https://www.ncbi.nlm.nih.gov/pubmed/24710520
http://dx.doi.org/10.1371/journal.pone.0093840
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author Miyagawa, Kazuaki
Yamazaki, Miwa
Kawai, Masanobu
Nishino, Jin
Koshimizu, Takao
Ohata, Yasuhisa
Tachikawa, Kanako
Mikuni-Takagaki, Yuko
Kogo, Mikihiko
Ozono, Keiichi
Michigami, Toshimi
author_facet Miyagawa, Kazuaki
Yamazaki, Miwa
Kawai, Masanobu
Nishino, Jin
Koshimizu, Takao
Ohata, Yasuhisa
Tachikawa, Kanako
Mikuni-Takagaki, Yuko
Kogo, Mikihiko
Ozono, Keiichi
Michigami, Toshimi
author_sort Miyagawa, Kazuaki
collection PubMed
description Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C. In Hyp mice, a murine model for X-linked hypophosphatemia (XLH), Phex deficiency results in the overproduction of FGF23 in osteocytes, which leads to hypophosphatemia and impaired vitamin D metabolism. In this study, to further clarify the abnormality in osteocytes of Hyp mice, we obtained detailed gene expression profiles in osteoblasts and osteocytes isolated from the long bones of 20-week-old Hyp mice and wild-type (WT) control mice. The expression of Fgf23, Dmp1, and Fam20c was higher in osteocytic cells than in osteoblastic cells in both genotypes, and was up-regulated in Hyp cells. Interestingly, the up-regulation of these genes in Hyp bones began before birth. On the other hand, the expression of Slc20a1 encoding the sodium/phosphate (Na(+)/Pi) co-transporter Pit1 was increased in osteoblasts and osteocytes from adult Hyp mice, but not in Hyp fetal bones. The direct effects of extracellular Pi and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on isolated osteoblastic and osteocytic cells were also investigated. Twenty-four-hour treatment with 10(−8) M 1,25(OH)(2)D(3) increased the expression of Fgf23 in WT osteoblastic cells but not in osteocytic cells. Dmp1 expression in osteocytic cells was increased due to the 24-hour treatment with 10 mM Pi and was suppressed by 10(−8) M 1,25(OH)(2)D(3) in WT osteocytic cells. We also found the up-regulation of the genes for FGF1, FGF2, their receptors, and Egr-1 which is a target of FGF signaling, in Hyp osteocytic cells, suggesting the activation of FGF/FGFR signaling. These results implicate the complex gene dysregulation in osteoblasts and osteocytes of Hyp mice, which might contribute to the pathogenesis.
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spelling pubmed-39778592014-04-11 Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice Miyagawa, Kazuaki Yamazaki, Miwa Kawai, Masanobu Nishino, Jin Koshimizu, Takao Ohata, Yasuhisa Tachikawa, Kanako Mikuni-Takagaki, Yuko Kogo, Mikihiko Ozono, Keiichi Michigami, Toshimi PLoS One Research Article Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C. In Hyp mice, a murine model for X-linked hypophosphatemia (XLH), Phex deficiency results in the overproduction of FGF23 in osteocytes, which leads to hypophosphatemia and impaired vitamin D metabolism. In this study, to further clarify the abnormality in osteocytes of Hyp mice, we obtained detailed gene expression profiles in osteoblasts and osteocytes isolated from the long bones of 20-week-old Hyp mice and wild-type (WT) control mice. The expression of Fgf23, Dmp1, and Fam20c was higher in osteocytic cells than in osteoblastic cells in both genotypes, and was up-regulated in Hyp cells. Interestingly, the up-regulation of these genes in Hyp bones began before birth. On the other hand, the expression of Slc20a1 encoding the sodium/phosphate (Na(+)/Pi) co-transporter Pit1 was increased in osteoblasts and osteocytes from adult Hyp mice, but not in Hyp fetal bones. The direct effects of extracellular Pi and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on isolated osteoblastic and osteocytic cells were also investigated. Twenty-four-hour treatment with 10(−8) M 1,25(OH)(2)D(3) increased the expression of Fgf23 in WT osteoblastic cells but not in osteocytic cells. Dmp1 expression in osteocytic cells was increased due to the 24-hour treatment with 10 mM Pi and was suppressed by 10(−8) M 1,25(OH)(2)D(3) in WT osteocytic cells. We also found the up-regulation of the genes for FGF1, FGF2, their receptors, and Egr-1 which is a target of FGF signaling, in Hyp osteocytic cells, suggesting the activation of FGF/FGFR signaling. These results implicate the complex gene dysregulation in osteoblasts and osteocytes of Hyp mice, which might contribute to the pathogenesis. Public Library of Science 2014-04-07 /pmc/articles/PMC3977859/ /pubmed/24710520 http://dx.doi.org/10.1371/journal.pone.0093840 Text en © 2014 Miyagawa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Miyagawa, Kazuaki
Yamazaki, Miwa
Kawai, Masanobu
Nishino, Jin
Koshimizu, Takao
Ohata, Yasuhisa
Tachikawa, Kanako
Mikuni-Takagaki, Yuko
Kogo, Mikihiko
Ozono, Keiichi
Michigami, Toshimi
Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice
title Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice
title_full Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice
title_fullStr Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice
title_full_unstemmed Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice
title_short Dysregulated Gene Expression in the Primary Osteoblasts and Osteocytes Isolated from Hypophosphatemic Hyp Mice
title_sort dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic hyp mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977859/
https://www.ncbi.nlm.nih.gov/pubmed/24710520
http://dx.doi.org/10.1371/journal.pone.0093840
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