Autophagy: A Key Regulator of Odontoblast Function, Pulp Homeostasis, and Regeneration

Autophagy is a crucial mechanism that ensures normal odontoblast function, as reported by Couve E [107]. Their study showed that the autophagic-lysosomal system was necessary to turnover and degrade subcellular components in odontoblasts in an age-related pattern. The impairment of this system resulted in decreased cell viability and dentinogenic secretory capacity [107]. Additionally, a study found that young and old cells differentially expressed autophagy- and aging-related molecules in response to LPS stimulation [108]. Peroxisome proliferator-activated receptor gamma (PPARγ) helps maintain pulp homeostasis during aging by activating autophagy, mitochondrial activity, and cell viability [108]. Yang et al. found that autophagy activation was significantly increased and correlated with the SDF-1α concentration in DPSC. Autophagy benefited SDF-1α-mediated DPSC migration by optimizing stress fiber assembly and focal adhesion formation [109]. Moreover, SDF-1α-loaded tooth fragment/silk fibroin scaffold significantly enhanced ectopic pulp regeneration and in situ pulp revascularization [109].

Autophagy also plays an essential role in crosstalk with pyroptosis and the NF-κB pathway. A recently published study showed that autophagy activation by rapamycin could reduce LPS-induced dental pulp cell pyroptosis [90]. 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 increases cell survival and dentinogenesis via the p-AMPK/AKT pathway [110]. Additionally, extracellular vesicles released by apoptotic cells could regulate the angiogenic activation of endothelial cells via the TFEB-autophagy pathway, benefiting dental pulp revascularization and regeneration [111].