Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels

Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels

Abstract Fibroblast growth factor 23 (FGF23) has been centric to the regulation of phosphate (Pi) metabolism; however, the regulatory network of FGF23 in osteocytes has not yet been defined in detail. We herein investigated the role of PTEN (phosphatase and tensin homolog deleted from chromosome 10)...

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Autores principales: Masanobu Kawai, Saori Kinoshita, Keiichi Ozono, Toshimi Michigami
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/7d2edd74e21949f0a5221a6d3d04539a
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spelling oai:doaj.org-article:7d2edd74e21949f0a5221a6d3d04539a2021-12-02T12:33:15ZLack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels10.1038/s41598-020-78692-62045-2322https://doaj.org/article/7d2edd74e21949f0a5221a6d3d04539a2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78692-6https://doaj.org/toc/2045-2322Abstract Fibroblast growth factor 23 (FGF23) has been centric to the regulation of phosphate (Pi) metabolism; however, the regulatory network of FGF23 in osteocytes has not yet been defined in detail. We herein investigated the role of PTEN (phosphatase and tensin homolog deleted from chromosome 10) in this regulation. We created mice lacking PTEN expression mainly in osteocytes by crossing Pten-flox mice with Dmp1-Cre mice. The lack of PTEN in the osteocytes of these mice was associated with decreased skeletal and serum intact FGF23 levels, which, in turn, resulted in reductions of urinary Pi excretion and elevations of serum Pi levels. Mechanistically, the knockdown of PTEN expression in osteoblastic UMR106 cells activated the AKT/mTORC1 (mechanistic target of rapamycin complex 1) pathway and this was associated with reductions in Fgf23 expression. Furthermore, the suppression of Fgf23 expression by PTEN knockdown or insulin simulation in UMR106 cells was partially restored by the treatment with the mTORC1 inhibitor, rapamycin. These results suggest that FGF23 expression in osteoblastic cells is in part regulated through the AKT/mTORC1 pathway and provide new insights into our understanding of the regulatory network of Pi metabolism.Masanobu KawaiSaori KinoshitaKeiichi OzonoToshimi MichigamiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Masanobu Kawai
Saori Kinoshita
Keiichi Ozono
Toshimi Michigami
Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
description Abstract Fibroblast growth factor 23 (FGF23) has been centric to the regulation of phosphate (Pi) metabolism; however, the regulatory network of FGF23 in osteocytes has not yet been defined in detail. We herein investigated the role of PTEN (phosphatase and tensin homolog deleted from chromosome 10) in this regulation. We created mice lacking PTEN expression mainly in osteocytes by crossing Pten-flox mice with Dmp1-Cre mice. The lack of PTEN in the osteocytes of these mice was associated with decreased skeletal and serum intact FGF23 levels, which, in turn, resulted in reductions of urinary Pi excretion and elevations of serum Pi levels. Mechanistically, the knockdown of PTEN expression in osteoblastic UMR106 cells activated the AKT/mTORC1 (mechanistic target of rapamycin complex 1) pathway and this was associated with reductions in Fgf23 expression. Furthermore, the suppression of Fgf23 expression by PTEN knockdown or insulin simulation in UMR106 cells was partially restored by the treatment with the mTORC1 inhibitor, rapamycin. These results suggest that FGF23 expression in osteoblastic cells is in part regulated through the AKT/mTORC1 pathway and provide new insights into our understanding of the regulatory network of Pi metabolism.
format article
author Masanobu Kawai
Saori Kinoshita
Keiichi Ozono
Toshimi Michigami
author_facet Masanobu Kawai
Saori Kinoshita
Keiichi Ozono
Toshimi Michigami
author_sort Masanobu Kawai
title Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
title_short Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
title_full Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
title_fullStr Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
title_full_unstemmed Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
title_sort lack of pten in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/7d2edd74e21949f0a5221a6d3d04539a
work_keys_str_mv AT masanobukawai lackofpteninosteocytesincreasescirculatingphosphateconcentrationsbydecreasingintactfibroblastgrowthfactor23levels
AT saorikinoshita lackofpteninosteocytesincreasescirculatingphosphateconcentrationsbydecreasingintactfibroblastgrowthfactor23levels
AT keiichiozono lackofpteninosteocytesincreasescirculatingphosphateconcentrationsbydecreasingintactfibroblastgrowthfactor23levels
AT toshimimichigami lackofpteninosteocytesincreasescirculatingphosphateconcentrationsbydecreasingintactfibroblastgrowthfactor23levels
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