Autophagy's Crucial Role in Odontoblast Function and Dental Pulp Regeneration

Autophagy plays a crucial role in maintaining the normal function of odontoblasts, according to Couve E's research [107]. Their study showed that the autophagic-lysosomal system was necessary for the turnover and degradation of subcellular components in odontoblasts, and impairment of this system resulted in decreased cell viability and dentinogenic secretory capacity [107]. Another study found that young and old cells showed differential expression of autophagy- and aging-related molecules in response to LPS stimulation [108]. Peroxisome proliferator-activated receptor gamma (PPARγ) was found to help maintain pulp homeostasis during aging by activating autophagy, mitochondrial activity, and cell viability [108]. Yang et al. [109] reported that autophagy activation was significantly increased and correlated with the SDF-1α concentration in DPSC, and autophagy benefited SDF-1α-mediated DPSCs migration by optimizing stress fiber assembly and focal adhesion formation. Moreover, SDF-1α-loaded tooth fragment/silk fibroin scaffold significantly enhanced ectopic pulp regeneration and in situ pulp revascularization [109].

Autophagy also has significant crosstalk with pyroptosis and the NF-κB pathway. A recent study showed that autophagy activation by rapamycin could reduce LPS-induced dental pulp cell pyroptosis [90], and the inhibition of autophagy exacerbated LPS-induced dental pulp cell pyroptosis. Further study revealed that 3-MA exacerbated LPS-mediated inhibition of IκBα expression and increased p-NF-κB expression, while rapamycin induced the opposite effects. This study suggested that modulating autophagy in dental pulp cells to balance pyroptosis could be a promising strategy for dental pulpitis therapy and dental pulp tissue regeneration.

Diabetes leads to irreversible damage and structural changes to dental pulp by down-regulating autophagy [110]. Rescuing autophagy by overexpression of C-myb can increase cell survival and dentinogenesis via the p-AMPK/AKT pathway [110]. In addition, extracellular vesicles released by apoptotic cells can regulate the angiogenic activation of endothelial cells via the TFEB-autophagy pathway, benefiting dental pulp revascularization and regeneration [111].