Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387448246> ?p ?o ?g. }
Showing items 1 to 65 of
65
with 100 items per page.
- W4387448246 abstract "Heterotopic ossification (HO) occurs following mechanical trauma and burns, or congenitally in patients suffering from fibrodysplasia ossificans progressiva (FOP). Recently, we demonstrated that inhibitors of phosphatidyl-inositol 3-kinase alpha (PI3Kα) may be a useful therapy for patients undergoing HO. In this study, using the already marketed BYL719/Alpelisib/Piqray drug, we have confirmed further these results, detailed the underlying mechanisms of action, and optimized the timing of the administration of BYL719. We found that BYL719 effectively prevents HO even when administered up to three to seven days after injury. We demonstrate in cell cultures and in a mouse model of HO that the major actions of BYL719 are on-target effects through the inhibition of PI3Kα, without directly affecting ACVR1 or FOP- inducing ACVR1R206H kinase activities. In vivo, we found that a lack of PI3Kα in progenitors at injury sites is sufficient to prevent HO. Moreover, time course assays in HO lesions demonstrate that BYL719 not only blocks osteochondroprogenitor specification, but also reduces the inflammatory response. BYL719 inhibits the migration, proliferation and expression of pro-inflammatory cytokines in monocytes and mast cells, suggesting that BYL719 hampers the hyper-inflammatory status of HO lesions. Altogether, these results highlight the potential of PI3Kα inhibition as a safe and effective therapeutic strategy for HO." @default.
- W4387448246 created "2023-10-10" @default.
- W4387448246 creator A5055584432 @default.
- W4387448246 date "2023-10-09" @default.
- W4387448246 modified "2023-10-11" @default.
- W4387448246 title "eLife assessment: PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossification" @default.
- W4387448246 doi "https://doi.org/10.7554/elife.91779.1.sa0" @default.
- W4387448246 hasPublicationYear "2023" @default.
- W4387448246 type Work @default.
- W4387448246 citedByCount "0" @default.
- W4387448246 crossrefType "peer-review" @default.
- W4387448246 hasAuthorship W4387448246A5055584432 @default.
- W4387448246 hasBestOaLocation W43874482461 @default.
- W4387448246 hasConcept C141071460 @default.
- W4387448246 hasConcept C150903083 @default.
- W4387448246 hasConcept C201750760 @default.
- W4387448246 hasConcept C203014093 @default.
- W4387448246 hasConcept C207001950 @default.
- W4387448246 hasConcept C2776914184 @default.
- W4387448246 hasConcept C2777995074 @default.
- W4387448246 hasConcept C2778842504 @default.
- W4387448246 hasConcept C2780650075 @default.
- W4387448246 hasConcept C28328180 @default.
- W4387448246 hasConcept C502942594 @default.
- W4387448246 hasConcept C60644358 @default.
- W4387448246 hasConcept C62478195 @default.
- W4387448246 hasConcept C71924100 @default.
- W4387448246 hasConcept C86554907 @default.
- W4387448246 hasConcept C86803240 @default.
- W4387448246 hasConcept C95444343 @default.
- W4387448246 hasConcept C98274493 @default.
- W4387448246 hasConceptScore W4387448246C141071460 @default.
- W4387448246 hasConceptScore W4387448246C150903083 @default.
- W4387448246 hasConceptScore W4387448246C201750760 @default.
- W4387448246 hasConceptScore W4387448246C203014093 @default.
- W4387448246 hasConceptScore W4387448246C207001950 @default.
- W4387448246 hasConceptScore W4387448246C2776914184 @default.
- W4387448246 hasConceptScore W4387448246C2777995074 @default.
- W4387448246 hasConceptScore W4387448246C2778842504 @default.
- W4387448246 hasConceptScore W4387448246C2780650075 @default.
- W4387448246 hasConceptScore W4387448246C28328180 @default.
- W4387448246 hasConceptScore W4387448246C502942594 @default.
- W4387448246 hasConceptScore W4387448246C60644358 @default.
- W4387448246 hasConceptScore W4387448246C62478195 @default.
- W4387448246 hasConceptScore W4387448246C71924100 @default.
- W4387448246 hasConceptScore W4387448246C86554907 @default.
- W4387448246 hasConceptScore W4387448246C86803240 @default.
- W4387448246 hasConceptScore W4387448246C95444343 @default.
- W4387448246 hasConceptScore W4387448246C98274493 @default.
- W4387448246 hasLocation W43874482461 @default.
- W4387448246 hasOpenAccess W4387448246 @default.
- W4387448246 hasPrimaryLocation W43874482461 @default.
- W4387448246 hasRelatedWork W180266173 @default.
- W4387448246 hasRelatedWork W1976064054 @default.
- W4387448246 hasRelatedWork W2082020414 @default.
- W4387448246 hasRelatedWork W2189378924 @default.
- W4387448246 hasRelatedWork W2244475179 @default.
- W4387448246 hasRelatedWork W2396519212 @default.
- W4387448246 hasRelatedWork W2980140195 @default.
- W4387448246 hasRelatedWork W3189081808 @default.
- W4387448246 hasRelatedWork W4293243323 @default.
- W4387448246 hasRelatedWork W204514590 @default.
- W4387448246 isParatext "false" @default.
- W4387448246 isRetracted "false" @default.
- W4387448246 workType "peer-review" @default.