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Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic...

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Autores principales: Uehara, Yasuaki, Tanaka, Yusuke, Zhao, Shuyang, Nikolaidis, Nikolaos M., Pitstick, Lori B., Wu, Huixing, Yu, Jane J., Zhang, Erik, Hasegawa, Yoshihiro, Noel, John G., Gardner, Jason C., Kopras, Elizabeth J., Haffey, Wendy D., Greis, Kenneth D., Guo, Jinbang, Woods, Jason C., Wikenheiser-Brokamp, Kathryn A., Kyle, Jennifer E., Ansong, Charles, Teitelbaum, Steven L., Inoue, Yoshikazu, Altinişik, Göksel, Xu, Yan, McCormack, Francis X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981730/
https://www.ncbi.nlm.nih.gov/pubmed/36864068
http://dx.doi.org/10.1038/s41467-023-36810-8
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author Uehara, Yasuaki
Tanaka, Yusuke
Zhao, Shuyang
Nikolaidis, Nikolaos M.
Pitstick, Lori B.
Wu, Huixing
Yu, Jane J.
Zhang, Erik
Hasegawa, Yoshihiro
Noel, John G.
Gardner, Jason C.
Kopras, Elizabeth J.
Haffey, Wendy D.
Greis, Kenneth D.
Guo, Jinbang
Woods, Jason C.
Wikenheiser-Brokamp, Kathryn A.
Kyle, Jennifer E.
Ansong, Charles
Teitelbaum, Steven L.
Inoue, Yoshikazu
Altinişik, Göksel
Xu, Yan
McCormack, Francis X.
author_facet Uehara, Yasuaki
Tanaka, Yusuke
Zhao, Shuyang
Nikolaidis, Nikolaos M.
Pitstick, Lori B.
Wu, Huixing
Yu, Jane J.
Zhang, Erik
Hasegawa, Yoshihiro
Noel, John G.
Gardner, Jason C.
Kopras, Elizabeth J.
Haffey, Wendy D.
Greis, Kenneth D.
Guo, Jinbang
Woods, Jason C.
Wikenheiser-Brokamp, Kathryn A.
Kyle, Jennifer E.
Ansong, Charles
Teitelbaum, Steven L.
Inoue, Yoshikazu
Altinişik, Göksel
Xu, Yan
McCormack, Francis X.
author_sort Uehara, Yasuaki
collection PubMed
description Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.
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spelling pubmed-99817302023-03-04 Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis Uehara, Yasuaki Tanaka, Yusuke Zhao, Shuyang Nikolaidis, Nikolaos M. Pitstick, Lori B. Wu, Huixing Yu, Jane J. Zhang, Erik Hasegawa, Yoshihiro Noel, John G. Gardner, Jason C. Kopras, Elizabeth J. Haffey, Wendy D. Greis, Kenneth D. Guo, Jinbang Woods, Jason C. Wikenheiser-Brokamp, Kathryn A. Kyle, Jennifer E. Ansong, Charles Teitelbaum, Steven L. Inoue, Yoshikazu Altinişik, Göksel Xu, Yan McCormack, Francis X. Nat Commun Article Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease. Nature Publishing Group UK 2023-03-02 /pmc/articles/PMC9981730/ /pubmed/36864068 http://dx.doi.org/10.1038/s41467-023-36810-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Uehara, Yasuaki
Tanaka, Yusuke
Zhao, Shuyang
Nikolaidis, Nikolaos M.
Pitstick, Lori B.
Wu, Huixing
Yu, Jane J.
Zhang, Erik
Hasegawa, Yoshihiro
Noel, John G.
Gardner, Jason C.
Kopras, Elizabeth J.
Haffey, Wendy D.
Greis, Kenneth D.
Guo, Jinbang
Woods, Jason C.
Wikenheiser-Brokamp, Kathryn A.
Kyle, Jennifer E.
Ansong, Charles
Teitelbaum, Steven L.
Inoue, Yoshikazu
Altinişik, Göksel
Xu, Yan
McCormack, Francis X.
Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
title Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
title_full Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
title_fullStr Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
title_full_unstemmed Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
title_short Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
title_sort insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981730/
https://www.ncbi.nlm.nih.gov/pubmed/36864068
http://dx.doi.org/10.1038/s41467-023-36810-8
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