Postdoctoral Research Asssociate University of Illinois at Chicago, Illinois, United States
Abstract: Dental caries is a common disease and represents a major public health problem. Untreated, it causes pain, leads to endodontic therapy, restoration or tooth loss. An alternative is therapeutic dentin regeneration. Yet, this remains clinically elusive. This study aims to enhance dentin regeneration in injured teeth by investigating the role of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in dental pulp stem cell (DPSC)-mediated dentinogenesis, particularly under inflammatory conditions. Additionally, we explore the potential of stem cell engineering to improve dentin regeneration. TrkB expression and activation in DPSCs were assessed during odontogenic differentiation, with and without inflammatory inducers such as TNFα, LPS, and LTA. A mouse pulp-capping/caries model was used for the in vivo evaluation of dentin formation, where CRISPR-engineered DPSCs overexpressing BDNF were transplanted into inflamed pulp tissue. Transcriptomic profiling was performed on TNFα-treated DPSCs, with and without TrkB antagonist CTX-B, to identify downstream pathways involved. TrkB expression and activation in DPSCs were significantly upregulated during odontogenic differentiation, especially under inflammatory stimulants by 301 ± 17, 320 ± 15.2, and 250 ± 19, respectively vs control 165 ± 12.4 (p < 0.01). In vivo, the transplantation of BDNF-overexpressing DPSCs led to enhanced dentin regeneration in the mouse model by increasing the dentin volume to 1241 ± 51 mg HA/ccm vs control 1169 ± 9 mg HA/ccm (p < 0.05). Transcriptomic analysis revealed that TrkB inhibition led to significant transcriptional alterations related to immune response, cytokine signaling, and extracellular matrix interactions. This study underscores the crucial role of BDNF and TrkB in DPSC-mediated dentin regeneration, particularly in the presence of inflammation. Through BDNF overexpression, stem cell engineering shows promise for enhancing dentin repair in injured teeth, providing potential therapeutic strategies for improved dental tissue regeneration.
