Autor según el artículo: 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
Departamento: Enginyeria Electrònica, Elèctrica i Automàtica
Autor/es de la URV: Junza Martínez, Alexandra / Yanes Torrado, Óscar
Palabras clave: 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
Resumen: 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.
Áreas temáticas: 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
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 2041-1723
Direcció de correo del autor: oscar.yanes@urv.cat alexandra.junza@urv.cat
Identificador del autor: 0000-0003-3695-7157 0000-0001-7205-0419
Fecha de alta del registro: 2024-10-12
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://www.nature.com/articles/s41467-020-14285-1
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Nature Communications. 11 (1): 431-
Referencia de l'ítem segons les normes 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
DOI del artículo: 10.1038/s41467-020-14285-1
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2020
Tipo de publicación: Journal Publications