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  Environmental arginine controls multinuclear giant cell metabolism and formation

Brunner, J. S., Vulliard, L., Hofmann, M., Kieler, M., Lercher, A., Vogel, A., et al. (2020). Environmental arginine controls multinuclear giant cell metabolism and formation. NATURE COMMUNICATIONS, 11(1). doi:10.1038/s41467-020-14285-1.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-C6B6-E Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C6B7-D
Genre: Journal Article

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 Creators:
Brunner, Julia S.1, Author
Vulliard, Loan1, Author
Hofmann, Melanie1, Author
Kieler, Markus1, Author
Lercher, Alexander1, Author
Vogel, Andrea1, Author
Russier, Marion2, Author              
Brueggenthies, Johanna B.2, Author              
Kerndl, Martina1, Author
Saferding, Victoria1, Author
Niederreiter, Birgit1, Author
Junza, Alexandra1, Author
Frauenstein, Annika3, Author              
Scholtysek, Carina1, Author
Mikami, Yohei1, Author
Klavins, Kristaps1, Author
Kroenke, Gerhard1, Author
Bergthaler, Andreas1, Author
O'Shea, John J.1, Author
Weichhart, Thomas1, Author
Meissner, Felix3, Author              Smolen, Josef S.1, AuthorCheng, Paul1, AuthorYanes, Oscar1, AuthorMenche, Joerg1, AuthorMurray, Peter J.2, Author              Sharif, Omar1, AuthorBlueml, Stephan1, AuthorSchabbauer, Gernot1, Author more..
Affiliations:
1external, ou_persistent22              
2Murray, Peter / Immunoregulation, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466696              
3Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Free keywords: MITOCHONDRIAL BIOGENESIS; MAMMALIAN TARGET; GENE ONTOLOGY; ARGINASE 1; OSTEOCLAST; ARTHRITIS; DESTRUCTION; HOMEOSTASIS; REGULATOR; IMMUNITY
 Abstract: Multinucleated giant cells (MGCs) are implicated in many diseases including schistosomiasis, sarcoidosis and arthritis. MGC generation is energy intensive to enforce membrane fusion and cytoplasmic expansion. Using receptor activator of nuclear factor kappa-Beta ligand (RANKL) induced osteoclastogenesis to model MGC formation, here we report RANKL cellular programming requires extracellular arginine. Systemic arginine restriction improves outcome in multiple murine arthritis models and its removal induces preosteoclast metabolic quiescence, associated with impaired tricarboxylic acid (TCA) cycle function and metabolite induction. Effects of arginine deprivation on osteoclastogenesis are independent of mTORC1 activity or global transcriptional and translational inhibition. Arginine scarcity also dampens generation of IL-4 induced MGCs. Strikingly, in extracellular arginine absence, both cell types display flexibility as their formation can be restored with select arginine precursors. These data establish how environmental amino acids control the metabolic fate of polykaryons and suggest metabolic ways to manipulate MGC-associated pathologies and bone remodelling. Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 11 (1) Sequence Number: - Start / End Page: - Identifier: ISSN: 2041-1723