Poly(Adenosine Phosphate Ribose) Polymerase 1 Inhibition Enhances Brain-derived Neurotrophic Factor Secretion in Dental Pulp Stem Cell–derived Odontoblastlike Cells

Abstract Introduction The nuclear enzyme poly(adenosine phosphate ribose) polymerase 1 (PARP-1) has been implicated in the maintenance and differentiation of several stem cells. The role of PARP-1 in dental pulp stem cell (DPSC) differentiation, especially in the context of its ability to modulate nerve regeneration factors, has not been investigated. Regeneration of neuronal components in pulp tissue is important for the assessment of tooth vitality. Brain-derived neurotrophic factor (BDNF) is known to play an integral signaling factor during nerve regeneration. In this study, we identified the role of PARP-1 in the modulation of BDNF in DPSC differentiation into odontoblastlike cells. Methods Human DPSCs were prepared from healthy molars and cultured in regular and osteogenic media treated with PARP-1 antagonist and PARP-1 exogeneous protein. Polymerase chain reaction and immunohistochemistry analysis for BDNF and various differentiation markers were performed. Results Our polymerase chain reaction results showed that differentiated cells show odontoblastlike properties because they express odontogenic markers such as dentin sialophosphoprotein and dentin matrix protein 1. Both PARP-1 inhibitor and protein did not affect odontogenic differentiation and proliferation because the number of the differentiated cells was unaffected, and the expression of dentin sialophosphoprotein and dentin matrix protein 1 was not significantly changed. There is the possibility that PARP-1 treatment induces DPSCs into the unique cell lineage. Some differentiated cells show a very unique morphology with large irregular cytoplasm and an oval nucleus. Moreover, PARP-1 inhibition significantly increased BDNF secretion in DPSC-derived odontoblastlike cells. This observation was also confirmed by immunohistochemistry. Conclusions Taken together, our results indicate PARP-1 as a negative regulator in BDNF secretion during odontogenic DPSC differentiation, showing its potential application for translational nerve regeneration strategies to improve dental pulp tissue vitality assessments.