Abstract： Objective To investigate the nucleotide-binding oligomerization domain-2(NOD-2)gene expression in deep caries and the effects of NOD-2 agonist muramyl dipeptide(MDP)on the differentiation of human dental pulp cells(hDPC). Methods NOD-2 gene level in deep caries and healthy pulp tissue was determined by real-time quantitative polymerase chain reaction(realtime-PCR). Realtime-PCR,Western blotting and immunofluorescence were performed to evaluate NOD-2 gene and protein expression. Dentin sialoprotein(DSP)protein level was assessed when hDPC were challenged by different concentrations of MDP for 24 hours, and sialophosphoprotein(DSPP), osteocalcin(OCN)mRNA and osteopontin(OPN)protein level were detected at different time points after incubation with 0.1 mg/L MDP. Results NOD-2 mRNA level was higher in pulp tissue of deep caries(0.2610±0.0824) than that in healthy controls(0.0024±0.0002),P<0.05.The expression of NOD-2 gene and protein increased in a time denpendent manner upon stimulation with MDP. Immunofluorescence confirmed that NOD-2 protein was located in cytoplasm. Moreover, 0.1 mg/L MDP augmented DSP protein level. DSPP and OCN mRNA were elevated with time and reached the peak at 12 h and down-regulated. OPN protein level also increased with time. Conclusions Dental pulp NOD-2 expression are up-regulated in pulp tissue of deep caries. MDP may be related to the differentiation of hDPC.