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

Yasuaki Uehara (), Yusuke Tanaka, Shuyang Zhao, Nikolaos M. Nikolaidis, Lori B. Pitstick, Huixing Wu, Jane J. Yu, Erik Zhang, Yoshihiro Hasegawa, John G. Noel, Jason C. Gardner, Elizabeth J. Kopras, Wendy D. Haffey, Kenneth D. Greis, Jinbang Guo, Jason C. Woods, Kathryn A. Wikenheiser-Brokamp, Jennifer E. Kyle, Charles Ansong, Steven L. Teitelbaum, Yoshikazu Inoue, Göksel Altinişik, Yan Xu () and Francis X. McCormack ()
Additional contact information
Yasuaki Uehara: University of Cincinnati College of Medicine
Yusuke Tanaka: University of Cincinnati College of Medicine
Shuyang Zhao: Cincinnati Children’s Hospital Medical Center
Nikolaos M. Nikolaidis: University of Cincinnati College of Medicine
Lori B. Pitstick: University of Cincinnati College of Medicine
Huixing Wu: University of Cincinnati College of Medicine
Jane J. Yu: University of Cincinnati College of Medicine
Erik Zhang: University of Cincinnati College of Medicine
Yoshihiro Hasegawa: University of Cincinnati College of Medicine
John G. Noel: University of Cincinnati College of Medicine
Jason C. Gardner: University of Cincinnati College of Medicine
Elizabeth J. Kopras: University of Cincinnati College of Medicine
Wendy D. Haffey: University of Cincinnati College of Medicine
Kenneth D. Greis: University of Cincinnati College of Medicine
Jinbang Guo: Cincinnati Children’s Hospital Medical Center
Jason C. Woods: Cincinnati Children’s Hospital Medical Center
Kathryn A. Wikenheiser-Brokamp: Cincinnati Children’s Hospital Medical Center
Jennifer E. Kyle: Pacific Northwest National Laboratory
Charles Ansong: Pacific Northwest National Laboratory
Steven L. Teitelbaum: Washington University School of Medicine
Yoshikazu Inoue: National Hospital Organization Kinki-Chuo Chest Medical Center
Göksel Altinişik: Pamukkale University
Yan Xu: Cincinnati Children’s Hospital Medical Center
Francis X. McCormack: University of Cincinnati College of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36810-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36810-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36810-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().