SMAD2 and osteogenesis imperfecta: A small study in type III patients with OI has documented upregulation of TGF‐β signaling, thus identifying this protein's central role in the pathogenesis of OI.(11) Type III patients exhibited increased phospho‐smad2 staining in bone sections, supporting the preclinical finding of increased TGF‐β activity in OI bone.(12) Regulation of SMAD phosphorylation was the most significantly upregulated molecular event, whereas TGF‐β activation was identified as the most significant upstream regulator.