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 Osteoclast Mitochondrial biogenesis Mammalian target Immunity Homeostasis Gene ontology Destruction Arthritis Arginase 1

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: alexandra.junza@urv.cat oscar.yanes@urv.cat

Identificador del autor: 0000-0001-7205-0419 0000-0003-3695-7157

Fecha de alta del registro: 2023-02-22

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: http://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.; Ke (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