Dual Role of Autophagy in Lipopolysaccharide-induced Preodontoblastic Cells

Abstract

Odontoblasts derive from neural crest-derived odontogenic mesenchymal cells, and they are an important barrier of defense for the host. Survival and immunity of odontoblasts play important roles in protecting the dentin-pulp structure. Autophagy can eliminate damaged organelles and recycle cellular components to facilitate cellular homeostasis. Autophagy can be activated with external stressors, such as starvation, hypoxia, and infection. In this study, the role of autophagy in inflamed odontoblasts was explored, and its possible mechanism was investigated. Cell viability was not affected by mild lipopolysaccharide (LPS) stimulation, and autophagy was activated during this process. Immunofluorescence of light chain 3 confirmed that autophagy was induced with LPS treatment. Early-stage autophagy inhibition resulted in down-regulated cell viability, contrary to the up-regulated cell viability at late-stage autophagy inhibition. Western blot suggested that p-Akt and survivin were not activated in the early stage, and they gradually increased and peaked in the late stage. Meanwhile, autophagy was down-regulated through the Akt/mTOR/survivin pathway in the late stage. Thus, autophagy has a dual role in inflamed odontoblasts, which indicates its importance in maintaining the microenvironment homeostasis of odontoblasts. Autophagy was induced as a survival mechanism in the early stage, and it decreased through the Akt/mTOR/survivin signaling pathway in the late stage.

Activation of mitophagy in inflamed odontoblasts

“…Odontoblasts play a pivotal role in dental pulp inflammation (Couve, Osorio, & Schmachtenberg, ). The previous studies of our group demonstrated that autophagy was of vital importance for survival and apoptosis of odontoblasts during inflammation (Pei et al, ; Wang, Pei, Chen, & Zhang, ). Autophagy was once considered nonselective; however, recent studies indicate that autophagy may be selective under certain circumstances (Farre & Subramani, ).…”

The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage

“…A number of studies have provided evidence of the fine-tuning of Atg12-Atg5 in relation to the intracellular redox state (Mai et al, 2012). Pei et al reported that the levels of Atg12-Atg5 were upregulated in a preodontoblast cell line (mDPC6T cells) after treatment with LPS for 6 h and 12 h but were downregulated after treatment with LPS for 24 h (Pei et al, 2015). …”

Autophagy in the dentin‐pulp complex against inflammation

“…The autophagy marker LC3 was detected within the odontoblast layer in human caries and pulpitis samples . Pei et al showed that LPSinduced autophagy played a dual role in the pre-odontoblast cell line mDPC6T (Pei et al, 2015). The cells could tolerate LPS stimulation, in which autophagy induction by LPS may be an even earlier prosurvival mechanism than the stellar prosurvival molecules Akt and survivin.…”