Disruption of Smad4 in odontoblasts and dental epithelial cells influences the phenotype of multiple keratocystic odontogenic tumors

Abstract

Keratocystic odontogenic tumors (KCOTs) are cystic epithelial neoplasms with a high recurrence rate. The molecular mechanisms underlying the initiation and progression of KCOTs are still largely unknown. Previous research showed that specific ablation of Smad4 in odontoblasts and dental epithelia resulted in spontaneous KCOTs in mice, and that constitutively activated Hedgehog (Hh) signaling was detected in the cyst epithelia of both Smad4Co/Co OC-Cre and Smad4Co/Co K5-Cre mice. Here, we ablated Smad4 in mouse odontoblasts and dental epithelia and compared the sizes and numbers of KCOTs. Both the number and size of KCOTs in Smad4Co/Co OC-Cre mice were larger than those in Smad4Co/Co K5-Cre mice, suggesting that paracrine signals from root odontoblasts play a more important role than those from Hertwig's epithelial root sheath (HERS) cells.