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

Autophagy plays a crucial role in maintaining the normal function of odontoblasts, as highlighted by Couve E's research [107]. Their findings suggest that the autophagic-lysosomal system is responsible for the turnover and degradation of subcellular components in odontoblasts, and its impairment leads to a decrease in cell viability and dentinogenic secretory capacity as age-related patterns emerge [107]. Another study revealed that autophagy- and aging-related molecules were differentially expressed in young and old cells in response to LPS stimulation [108]. Peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining pulp homeostasis during aging by activating autophagy, mitochondrial activity, and cell viability [108]. Yang et al.'s study further demonstrated that autophagy activation was significantly increased and correlated with the SDF-1α concentration in DPSC. Autophagy optimized stress fibre assembly and focal adhesion formation, which, in turn, benefited SDF-1α-mediated DPSC migration [109]. The use of SDF-1α-loaded tooth fragment/silk fibroin scaffold also significantly enhanced ectopic pulp regeneration and in situ pulp revascularization [109].

Autophagy also interacts with pyroptosis and the NF-κB pathway. A recent study shows that rapamycin-induced autophagy activation could reduce LPS-induced dental pulp cell pyroptosis [90]. Conversely, inhibition of autophagy exacerbates LPS-induced dental pulp cell pyroptosis. Further analysis revealed that 3-MA exacerbates LPS-mediated inhibition of IκBα expression and increases p-NF-κB expression, while rapamycin induces the opposite effects. Thus, regulating autophagy in dental pulp cells to balance pyroptosis could potentially be a promising strategy for dental pulpitis therapy and dental pulp tissue regeneration.

Diabetes causes irreversible damage and structural changes to dental pulp by down-regulating autophagy [110]. However, overexpression of C-myb rescues autophagy, leading to increased cell survival and dentinogenesis via the p-AMPK/AKT pathway [110]. Additionally, 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].