Palovarotenesuppressespost-traumaticchondrogenesisandosteogenesisandmitigatedtrauma-inducedectopicboneformation.Palovaroteneinhibitssubcutaneousandintramuscularheterotopicossification(HO)inmice.Palovaroteneisgivenorallyfor14daysat1mg/kg/daystartingonpost-operativeday(POD)1orPOD-5,andHOamount,wounddehiscenceandrelatedprocessesaremonitoredforupto84dayspostinjury.Comparedtovehicle-controlanimals,PalovarotenesignificantlydecreasesHOby50to60%regardlessofwhenthetreatmentstartedandifinfectionispresent.Startingfromday1ofinjury,halfoftheAcvr1cR206H/+micearetreatedwithPalovarotenebydailygavagefor14daysandtheotherhalfreceivedvehicleascontrol.AnalysisbymCTand3Dimagereconstructionatday14showsthatlargeHOtissuemasseshaveformedinthetargetedlegofAcvr1cR206H/+mutantmicereceivingvehicle,butHOformationisgreatlydiminishedinPalovarotene-treatedcompanionsbymorethan80%basedonbonevolume/totalvolumequantification.
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