MassIVE MSV000091302

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

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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 kappa B (NF-kB) 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. [doi:10.25345/C5JW86X6Z] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: lipidomics ; pulmonary disease ; microliths

Contact

Principal Investigators:
(in alphabetical order) 		Francis X. McCormack, University of Cincinnati, USA
Submitting User: alchemistmatt

Publications

Uehara Y, Tanaka Y, Zhao S, Nikolaidis NM, Pitstick LB, Wu H, Yu JJ, Zhang E, Hasegawa Y, Noel JG, Gardner JC, Kopras EJ, Haffey WD, Greis KD, Guo J, Woods JC, Wikenheiser-Brokamp KA, Kyle JE, Ansong C, Teitelbaum SL, Inoue Y, Altini?ik G, Xu Y, McCormack FX.
Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis.
Nat Commun. 2023 Mar 2;14(1):1205. Epub 2023 Mar 2.

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