ABS 006: Runx2 Activity in Mature Odontoblast Regulate Secretion and Maintenance of Dentin

Sarah Jasser, Javeed Farooqi, Farrah Memon, Anabia Javed, Laiba Asif, Amjad Javed

Van Wickle (2025) Volume 1, ABS 006

Introduction: Dentin is essential for protecting dental pulp stem cells from invading oral pathogens. Teeth with low levels of dentin are susceptible to caries, infections, and fractures. Nearly half of the adults in the US suffer from periodontitis. Dentin is synthesized and secreted by odontoblasts. Runx2 transcription factor is the master regulator of osteoblast differentiation and bone formation. The global deletion of the Runx2 gene results in failure of bone and tooth development. However, the odontoblast specific role of Runx2 in synthesizing and maintaining postnatal dentin remains unknown.

Methods: Runx2 gene floxed, and OC-Cre transgenic mouse models were used to assess the effect of Runx2 deletion in odontoblasts. Radiological, histological, and qPCR approaches were employed to quantify changes in the dentin matrix.

Results: We initially confirmed the mature odontoblast restricted activity of the OC-Cre by using Td-reporter mice. The homozygous (Runx2F/F;OC-Cre) mice were born alive and showed comparable tooth development to WT littermates. We observed similar sizes and shapes of the erupted incisors and molars. The changes in the amount of postnatal dentin in the molars and continuously growing incisors were quantified by µCT of 1-month old littermates. The dentin was increased in the mandibular molars and incisors of homozygous mice. Double calcein labeling revealed a significant increase in dentin synthesis by Runx2-deficient odontoblasts. H&E staining showed that the odontoblast polarization was impaired in the homozygous. Consistent with these observations, qPCR showed a decrease in the expression of odontoblast marker genes (DMP1, DSPP, OC, Sp7).

Discussion: Runx2 exerts a differential control of mineralizing cells. Runx2 deletion increased dentin secretion in 1-month of age. Runx2 activity is necessary to maintain pulp cavity in the continually growing incisors