Evidence map›Paper›PMID 38951609›Full record

ArticleThe EMBO journal2024

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

Arianna Mangiavacchi, Gabriele Morelli, Sjur Reppe, Alfonso Saera-Vila, Peng Liu, Benjamin Eggerschwiler, Huoming Zhang, Dalila Bensaddek, Elisa A Casanova, Carolina Medina Gomez and 8 more

Erratum issuedAbstract read
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Arianna MangiavacchiKing 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.ORCID http://orcid.org/0000-0002-9551-9344
Gabriele MorelliKing Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia.ORCID http://orcid.org/0000-0001-6297-6373
Sjur ReppeOslo University Hospital, Department of Medical Biochemistry, Oslo, Norway.ORCID http://orcid.org/0000-0002-4330-5379
Alfonso Saera-VilaSequentia Biotech, Carrer Comte D'Urgell 240, Barcelona, 08036, Spain.
Peng LiuKing Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia.
Benjamin EggerschwilerDepartment of Trauma, University Hospital Zurich, Sternwartstrasse 14, 8091, Zurich, Switzerland.
Huoming ZhangCore Labs, King Abdullah University of Science and Technology (KAUST), Thuwal, 23500-6900, Kingdom of Saudi Arabia.
Dalila BensaddekCore Labs, King Abdullah University of Science and Technology (KAUST), Thuwal, 23500-6900, Kingdom of Saudi Arabia.
Elisa A CasanovaDepartment of Trauma, University Hospital Zurich, Sternwartstrasse 14, 8091, Zurich, Switzerland.
Carolina Medina GomezDepartment of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands.
Vid PrijateljDepartment of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands.ORCID http://orcid.org/0000-0002-9463-3962
Francesco Della ValleKing Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia.ORCID http://orcid.org/0000-0001-9889-1283
Nazerke AtinbayevaKing Abdullah University of Science and Technology (KAUST), Biological Environmental Science and Engineering Division, Thuwal, 23500-6900, Kingdom of Saudi Arabia.ORCID http://orcid.org/0000-0002-9793-340X
Juan Carlos Izpisua BelmonteAltos Labs, San Diego, CA, USA.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands.
Paolo CinelliDepartment of Trauma, University Hospital Zurich, Sternwartstrasse 14, 8091, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-0163-9055
Kaare Morten Gautvik *Lovisenberg Diaconal Hospital, Unger-Vetlesen Institute, Oslo, Norway.ORCID http://orcid.org/0000-0002-3458-6113
Valerio Orlando *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.ORCID http://orcid.org/0000-0002-4906-8511

Funding

European union project OSTEOGENE FP6-502491King Abdullah University of Science and Technology (KAUST) BAS/1/1037-01-01Oslo University Hospital, Ulleval 29750104ZonMw (Netherlands Organisation for Health Research and Development) 016.136.367
6 · The paper itself

Abstract

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.

Indexed as

eIF-2 KinaseInflammationLong Interspersed Nucleotide ElementsMesenchymal Stem CellsAnimalsCalcification, PhysiologicHumansMiceOsteoblastsEIF2AK2 protein, humaneIF-2 KinasedsRNAInflammationOsteoblastPKRTransposable Elements

Identifiers

PMID38951609
PMCPMC11377738

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.