Articles producció científica> Enginyeria Electrònica, Elèctrica i Automàtica

Environmental arginine controls multinuclear giant cell metabolism and formation

  • Identification data

    Identifier: imarina:6097009
    Authors:
    Brunner, Julia SVulliard, LoanHofmann, MelanieKieler, MarkusLercher, AlexanderVogel, AndreaRussier, MarionBrueggenthies, Johanna BKerndl, MartinaSaferding, VictoriaNiederreiter, BirgitJunza, AlexandraFrauenstein, AnnikaScholtysek, CarinaMikami, YoheiKlavins, KristapsKroenke, GerhardBergthaler, AndreasO'Shea, John JWeichhart, ThomasMeissner, FelixSmolen, Josef SCheng, PaulYanes, OscarMenche, JoergMurray, Peter JSharif, OmarBlueml, StephanSchabbauer, Gernot
    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.
  • Others:

    Author, as appears in the article.: Brunner, Julia S; Vulliard, Loan; Hofmann, Melanie; Kieler, Markus; Lercher, Alexander; Vogel, Andrea; Russier, Marion; Brueggenthies, Johanna B; Kerndl, Martina; Saferding, Victoria; Niederreiter, Birgit; Junza, Alexandra; Frauenstein, Annika; Scholtysek, Carina; Mikami, Yohei; Klavins, Kristaps; Kroenke, Gerhard; Bergthaler, Andreas; O'Shea, John J; Weichhart, Thomas; Meissner, Felix; Smolen, Josef S; Cheng, Paul; Yanes, Oscar; Menche, Joerg; Murray, Peter J; Sharif, Omar; Blueml, Stephan; Schabbauer, Gernot
    Department: Enginyeria Electrònica, Elèctrica i Automàtica
    URV's Author/s: Junza Martínez, Alexandra / Yanes Torrado, Óscar
    Keywords: Regulator Rank ligand Osteogenesis Osteoclasts Osteoclast Mitochondrial biogenesis Mice, inbred c57bl Mice Mechanistic target of rapamycin complex 1 Mammalian target Interleukin-4 Immunity Humans Homeostasis Giant cells Gene ontology Female Destruction Citric acid cycle Bone remodeling Arthritis Arginine Arginase 1 Animals
    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.
    Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Planejamento urbano e regional / demografia Physics and astronomy (miscellaneous) Physics and astronomy (all) Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Interdisciplinar Geociências General physics and astronomy General medicine General chemistry General biochemistry,genetics and molecular biology Farmacia Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência da computação Chemistry (miscellaneous) Chemistry (all) Biotecnología Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Astronomia / física Antropologia / arqueologia
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 2041-1723
    Author's mail: oscar.yanes@urv.cat alexandra.junza@urv.cat
    Author identifier: 0000-0003-3695-7157 0000-0001-7205-0419
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.nature.com/articles/s41467-020-14285-1
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Nature Communications. 11 (1): 431-
    APA: Brunner, Julia S; Vulliard, Loan; Hofmann, Melanie; Kieler, Markus; Lercher, Alexander; Vogel, Andrea; Russier, Marion; Brueggenthies, Johanna B; Kern (2020). Environmental arginine controls multinuclear giant cell metabolism and formation. Nature Communications, 11(1), 431-. DOI: 10.1038/s41467-020-14285-1
    Article's DOI: 10.1038/s41467-020-14285-1
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2020
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry, Genetics and Molecular Biology (Miscellaneous),Chemistry (Miscellaneous),Multidisciplinary Sciences,Physics and Astronomy (Miscellaneous)
    Regulator
    Rank ligand
    Osteogenesis
    Osteoclasts
    Osteoclast
    Mitochondrial biogenesis
    Mice, inbred c57bl
    Mice
    Mechanistic target of rapamycin complex 1
    Mammalian target
    Interleukin-4
    Immunity
    Humans
    Homeostasis
    Giant cells
    Gene ontology
    Female
    Destruction
    Citric acid cycle
    Bone remodeling
    Arthritis
    Arginine
    Arginase 1
    Animals
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Psicología
    Planejamento urbano e regional / demografia
    Physics and astronomy (miscellaneous)
    Physics and astronomy (all)
    Odontología
    Nutrição
    Multidisciplinary sciences
    Multidisciplinary
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Matemática / probabilidade e estatística
    Interdisciplinar
    Geociências
    General physics and astronomy
    General medicine
    General chemistry
    General biochemistry,genetics and molecular biology
    Farmacia
    Engenharias iv
    Educação física
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência da computação
    Chemistry (miscellaneous)
    Chemistry (all)
    Biotecnología
    Biodiversidade
    Biochemistry, genetics and molecular biology (miscellaneous)
    Biochemistry, genetics and molecular biology (all)
    Astronomia / física
    Antropologia / arqueologia
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