Environmental arginine controls multinuclear giant cell metabolism and formation

Brunner JS, Vulliard L, Hofmann M, Kieler M, Lercher A, Vogel A, Russier M, Brüggenthies JB, Kerndl M, Saferding V, Niederreiter B, Junza A, Frauenstein A, Scholtysek C, Mikami Y, Klavins K, Krönke G, Bergthaler A, O’Shea JJ, Weichhart T, Meissner F, Smolen JS, Cheng P, Yanes O, Menche J, Murray PJ, Sharif O, Blüml S, Schabbauer G (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 11

Article Number: 431

Journal Issue: 1

DOI: 10.1038/s41467-020-14285-1

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-Β 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.

Authors with CRIS profile

Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Medizinische Universität Wien AT Austria (AT) Christian Doppler Forschungsgesellschaft AT Austria (AT) Österreichische Akademie der Wissenschaften AT Austria (AT) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) US United States (USA) (US) Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry DE Germany (DE) Bio-Cancer Treatment International Limited CN China (CN)

How to cite

APA:

Brunner, J.S., Vulliard, L., Hofmann, M., Kieler, M., Lercher, A., Vogel, A.,... Schabbauer, G. (2020). Environmental arginine controls multinuclear giant cell metabolism and formation. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-14285-1

MLA:

Brunner, Julia S., et al. "Environmental arginine controls multinuclear giant cell metabolism and formation." Nature Communications 11.1 (2020).

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