Inhibition of phosphatidylinositol 3-kinase α (PI3Kα) prevents heterotopic ossification.

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 Acvr1^R206H allele. Further, the efficacy of PI3Kα inhibitors was evaluated in transgenic mice expressing Acvr1^Q207D . Mice treated daily or intermittently wi

SUBMITTER: Valer JA 

PROVIDER: S-EPMC6728602 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature