Nearly half of the adults in the US suffer from periodontitis. 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. 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 formation and embryonic lethality. However, the role of Runx2 in odontoblasts for synthesizing and maintaining postnatal dentin needs to be better understood.  To answer this question, we have generated a Runx2 gene floxed model. Runx2 gene was deleted in mature odontoblasts by using OC-Cre mice. We confirmed OC-Cre activity in mature odontoblast by Td-reporter. The homozygous mice were born alive with normal development and eruption of incisors and molars. The changes in the dentin synthesis will be assessed by micro-computed tomography (µCT) of load-bearing molars and continuously growing incisors at 2-week, 1-month, and 3-month time points. Disruption in odontoblasts differentiation due to lack of Runx2 will be investigated by changes in expression of dentin marker genes (DMP1, DSPP, OC, Sp7) by qPCR and RNA-Scope. TUNNEL staining will be used to know the involvement of Runx2 in odontoblast survival and death. Odontoblast differentiation, polarization, and the maturation of dentin tubules will be assessed by H&E staining. Double Calcein labeling will be used to quantify dynamic dentin synthesis. While tooth development is expected to progress normally, we anticipate a significant decrease in odontoblast gene expression, polarization, and dentin synthesis.