LINE-1 RNA triggers matrix formation in bone cells via a PKR-mediated inflammatory response.

Autor:	Mangiavacchi A; King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia. Arianna.mangiavacchi@kaust.edu.sa., Morelli G; King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia., Reppe S; Oslo University Hospital, Department of Medical Biochemistry, Oslo, Norway.; Lovisenberg Diaconal Hospital, Unger-Vetlesen Institute, Oslo, Norway.; Oslo University Hospital, Department of Plastic and Reconstructive Surgery, Oslo, Norway., Saera-Vila A; Sequentia Biotech, Carrer Comte D'Urgell 240, Barcelona, 08036, Spain., Liu P; King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia., Eggerschwiler B; Department of Trauma, University Hospital Zurich, Sternwartstrasse 14, 8091, Zurich, Switzerland.; Life Science Zurich Graduate School, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland., Zhang H; Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal, 23500-6900, Kingdom of Saudi Arabia., Bensaddek D; Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal, 23500-6900, Kingdom of Saudi Arabia., Casanova EA; Department of Trauma, University Hospital Zurich, Sternwartstrasse 14, 8091, Zurich, Switzerland., Medina Gomez C; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands., Prijatelj V; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands., Della Valle F; King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia.; Altos Labs, San Diego, CA, USA., Atinbayeva N; King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia., Izpisua Belmonte JC; Altos Labs, San Diego, CA, USA., Rivadeneira F; Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands., Cinelli P; Department of Trauma, University Hospital Zurich, Sternwartstrasse 14, 8091, Zurich, Switzerland.; Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland., Gautvik KM; Lovisenberg Diaconal Hospital, Unger-Vetlesen Institute, Oslo, Norway., Orlando V; King Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia. Valerio.orlando@kaust.edu.sa.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2024 Sep; Vol. 43 (17), pp. 3587-3603. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1038/s44318-024-00143-z
Abstrakt:	Transposable elements (TEs) are mobile genetic modules of viral derivation that have been co-opted to become modulators of mammalian gene expression. TEs are a major source of endogenous dsRNAs, signaling molecules able to coordinate inflammatory responses in various physiological processes. Here, we provide evidence for a positive involvement of TEs in inflammation-driven bone repair and mineralization. In newly fractured mice bone, we observed an early transient upregulation of repeats occurring concurrently with the initiation of the inflammatory stage. In human bone biopsies, analysis revealed a significant correlation between repeats expression, mechanical stress and bone mineral density. We investigated a potential link between LINE-1 (L1) expression and bone mineralization by delivering a synthetic L1 RNA to osteoporotic patient-derived mesenchymal stem cells and observed a dsRNA-triggered protein kinase (PKR)-mediated stress response that led to strongly increased mineralization. This response was associated with a strong and transient inflammation, accompanied by a global translation attenuation induced by eIF2α phosphorylation. We demonstrated that L1 transfection reshaped the secretory profile of osteoblasts, triggering a paracrine activity that stimulated the mineralization of recipient cells. (© 2024. The Author(s).)
Databáze:	MEDLINE
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