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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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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. |
format | Online Article Text |
id | pubmed-3977859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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