Previous reports demonstrated that TLR and IL1R1 signaling, activated by LPS and IL-1β, respectively, enhanced BMP-induced phosphorylation and/or transcriptional activity of Smad1/5/8 in fibroblasts from FOP patients [31] and other cell types [28,29,36,37] but did not utilize intramuscular FAPs. Here, SMAD1 is linked to fibrodysplasia ossificans progressiva.