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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: 431. doi:10.1038/s41467-020-14285-1.

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 Urheber:
Brunner, Julia S.1, Autor
Vulliard, Loan1, Autor
Hofmann, Melanie1, Autor
Kieler, Markus1, Autor
Lercher, Alexander1, Autor
Vogel, Andrea1, Autor
Russier, Marion2, Autor           
Brueggenthies, Johanna B.2, Autor           
Kerndl, Martina1, Autor
Saferding, Victoria1, Autor
Niederreiter, Birgit1, Autor
Junza, Alexandra1, Autor
Frauenstein, Annika3, Autor           
Scholtysek, Carina1, Autor
Mikami, Yohei1, Autor
Klavins, Kristaps1, Autor
Kroenke, Gerhard1, Autor
Bergthaler, Andreas1, Autor
O'Shea, John J.1, Autor
Weichhart, Thomas1, Autor
Meissner, Felix3, Autor           Smolen, Josef S.1, AutorCheng, Paul1, AutorYanes, Oscar1, AutorMenche, Joerg1, AutorMurray, Peter J.2, Autor           Sharif, Omar1, AutorBlueml, Stephan1, AutorSchabbauer, Gernot1, Autor mehr..
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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Schlagwörter: MITOCHONDRIAL BIOGENESIS; MAMMALIAN TARGET; GENE ONTOLOGY; ARGINASE 1; OSTEOCLAST; ARTHRITIS; DESTRUCTION; HOMEOSTASIS; REGULATOR; IMMUNITY
 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2020
 Publikationsstatus: Erschienen
 Seiten: 15
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000511464000010
DOI: 10.1038/s41467-020-14285-1
 Art des Abschluß: -

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Titel: NATURE COMMUNICATIONS
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Seiten: - Band / Heft: 11 Artikelnummer: 431 Start- / Endseite: - Identifikator: ISSN: 2041-1723