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http://hdl.handle.net/2445/146565
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DC Field | Value | Language |
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dc.contributor.author | Valer, José Antonio | - |
dc.contributor.author | Sánchez de Diego, Cristina | - |
dc.contributor.author | Gamez Molina, Beatriz | - |
dc.contributor.author | Mishina, Yuji | - |
dc.contributor.author | Rosa López, José Luis | - |
dc.contributor.author | Ventura Pujol, Francesc | - |
dc.date.accessioned | 2019-12-12T16:12:39Z | - |
dc.date.available | 2019-12-12T16:12:39Z | - |
dc.date.issued | 2019-08-02 | - |
dc.identifier.issn | 1757-4676 | - |
dc.identifier.uri | http://hdl.handle.net/2445/146565 | - |
dc.description.abstract | Heterotopic ossification (HO) is the pathological formation of ectopic endochondral bone within soft tissues. HO occurs following mechanical trauma, burns, or congenitally in patients suffering from fibrodysplasia ossificans progressiva (FOP). FOP patients carry a conserved mutation in ACVR1 that becomes neomorphic for activin A responses. Here, we demonstrate the efficacy of BYL719, a PI3Kα inhibitor, in preventing HO in mice. We found that PI3Kα inhibitors reduce SMAD, AKT, and mTOR/S6K activities. Inhibition of PI3Kα also impairs skeletogenic responsiveness to BMPs and the acquired response to activin A of the Acvr1R206H allele. Further, the efficacy of PI3Kα inhibitors was evaluated in transgenic mice expressing Acvr1Q207D . Mice treated daily or intermittently with BYL719 did not show ectopic bone or cartilage formation. Furthermore, the intermittent treatment with BYL719 was not associated with any substantial side effects. Therefore, this work provides evidence supporting PI3Kα inhibition as a therapeutic strategy for HO. | - |
dc.format.extent | 13 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | EMBO Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.15252/emmm.201910567 | - |
dc.relation.ispartof | EMBO Molecular Medicine, 2019, vol. 11, num. 9, p. e10567 | - |
dc.relation.uri | https://doi.org/10.15252/emmm.201910567 | - |
dc.rights | cc-by (c) Valer, José Antonio et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Malalties dels ossos | - |
dc.subject.classification | Ossificació | - |
dc.subject.classification | Proteïnes quinases | - |
dc.subject.other | Bone diseases | - |
dc.subject.other | Ossification | - |
dc.subject.other | Protein kinases | - |
dc.title | Inhibition of phosphatidylinositol 3-kinase α (PI3Kα) prevents heterotopic ossification | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 693166 | - |
dc.date.updated | 2019-12-12T16:12:39Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31373426 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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693166.pdf | 3.45 MB | Adobe PDF | View/Open |
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