SMAD3 and osteoarthritis: More recently, mutations in the gene encoding SMAD3, which is an essential effector of TGFβ signaling, cause the newly described aneurysms-osteoarthritis syndrome (AOS), which is characterized by aortic aneurysms with early-onset osteoarthritis (van de Laar et al., 2011; van de Laar et al., 2012).