Autophagy in resin monomer-initiated toxicity of dental mesenchymal cells: a novel therapeutic target of N-acetyl cysteine

Abstract

Dental restorative biomaterials are commonly used to restore the teeth impaired by caries, erosion, or fracture. Resin monomers released from polymerized restorative composite materials could disturb cell viability and cause toxicity of oral eukaryotic cells, which remains a medical challenge. However, the intracellular processes or underlying mechanisms of resin monomer-mediated toxicity and the potential preventive/therapeutic strategy are still far from clear. The present study aimed to determine the role of autophagy in resin monomer triethylene glycol dimethacrylate (TEGDMA)-induced cytotoxicity and explore autophagy as a potential therapeutic target of anti-oxidant N-acetyl cysteine (NAC) in vitro and ex vivo. The results showed that TEGDMA exposure resulted in several specific features of autophagy in human dental mesenchymal cells (DMCs), including the formation of acidic vesicular organelles, appearance of autophagic vacuoles, and LC3-II accumulation. By pharmacological and genetic approaches, the inhibition of autophagy significantly prevented TEGDMA-induced apoptosis in DMCs. Moreover, the autophagy activated by TEGDMA occurred via the AMPK/mTOR pathway, which could be abrogated by NAC pretreatment. More importantly, the tooth slice organ culture model provided further evidence of autophagy involvement in TEGDMA-triggered dental mesenchymal tissue toxicity and as a therapeutic target of NAC ex vivo. Our findings provide novel insights into the mechanisms of resin monomer-mediated toxicity and highlight autophagy as a promising therapeutic target of NAC for improving dental restorative biomaterials that enable dental tissue protection.