Autophagy regulates odontoblast differentiation by suppressing NF-κB activation in an inflammatory environment

Abstract

Odontoblasts are derived from dental papilla mesenchymal cells and have an important role in defense against bacterial infection, whereas autophagy can recycle long-lived proteins and damaged organelles to sustain cellular homeostasis. Thus, this study explores the role of autophagy in odontoblast differentiation with lipopolysaccharide (LPS) stimulation in vitro and the colocalization of p-NF-κB and LC3 in caries teeth. The odontoblasts differentiation was enhanced through LPS stimulation, and this outcome was reflected in the increased number of mineralized nodules and alkaline phosphatase (ALP) activity. The expression levels of the autophagy markers LC3, Atg5, Beclin1 and TFE3 increased time dependently, as well along with the amount of autophagosomes and autophagy fluxes. This result suggests that autophagy was enhanced in odontoblasts cultured with mineralized-induced media containing LPS. To confirm the role of autophagy in differentiated odontoblasts with LPS stimulation, chloroquine (CQ) or rapamycin were used to either block or enhance autophagy. The number of mineralized nodules decreased when autophagy was inhibited, but this number increased with rapamycin treatment. Phosphorylated nuclear factor-κB (NF-κB) expression was negatively related to autophagy and could inhibit odontoblast differentiation. Furthermore, p-NF-κB and LC3 colocalization could be detected in cells stimulated with LPS. The nucleus translocation of p-NF-κB in odontoblasts was enhanced when autophagy was inhibited by Atg5 small interfering RNA. In addition, the colocalization of p-NF-κB and LC3 in odontoblasts and sub-odontoblastic layers was observed in caries teeth with reactionary dentin. Therefore, our findings provide a novel insight into the role of autophagy in regulating odontoblast differentiation by suppressing NF-κB activation in inflammatory environments.

Deferoxamine-Induced Migration and Odontoblast Differentiation via ROS-Dependent Autophagy in Dental Pulp Stem Cells

“…Recent studies have discovered that inflammatory cytokine could attenuate the odontoblastic differentiation of dental stem cells [35]. Furthermore, Pei et al reported that autophagy induced by inflammatory environment is critical in regulating odontoblastic differentiation [36]. More highly reserved ATGs have been identified in regulating the odontoblastic differentiation of stem cells [37].…”

Roles of High Mobility Group Box 1 in Cardiovascular Calcification

“…However, most of the work thus far has focused on the role of autophagy in osteoblastic differentiation. One study reported that autophagy is involved in the osteogenic differentiation of odontoblasts [131] and human osteoblast associated with the titanium-based dental implants [132]. In mesenchymal stem cells (MSCs), autophagy is induced by forkhead box O3 (FOXO3) to reduce ROS resulting from the increased mitochondrial respiration that occurs during osteoblast differentiation [133] and may regulate osteogenic differentiation via AMPK/Akt/mTOR signaling [134].…”

Lipopolysaccharide‐induced DNA damage response activates nuclear factor κB signalling pathway via GATA4 in dental pulp cells

“…Accumulating evidence shows that LPS causes inflammatory reactions in DPCs and promotes translocation of p65 from the cytoplasm to the nucleus (Pei et al 2016). Accumulating evidence shows that LPS causes inflammatory reactions in DPCs and promotes translocation of p65 from the cytoplasm to the nucleus (Pei et al 2016).…”