SMAD3 and aneurysm: Smad3-null mice and chondrocyte-specific Smad3 CKO mice exhibit articular cartilage degeneration and automatically develop OA.57–59 Mutations of Smad3 in human caused aneurysms–osteoarthritis syndrome,15,60,61 which is presenting with aneurysms, mild craniofacial features, and skeletal and cutaneous anomalies.