Elsevier

Journal of Endodontics

Volume 46, Issue 10, October 2020, Pages 1403-1413
Journal of Endodontics

Review Article
Regulated Cell Death in Pulpitis

https://doi.org/10.1016/j.joen.2020.07.006Get rights and content

Abstract

Regulated cell death (RCD) is a preferred term inclusive of all modes of cell death regulated by multiple intracellular signal transduction pathways under physiological and pathologic conditions. Although cell death programs ensure correct growth and developmental processes as well as protect the host against microbial pathogens, some necrotic cell death pathways, such as pyroptosis, NETosis, and necroptosis, release intracellular damage-associated molecular patterns and inflammatory cytokines, thereby skewing the milieu toward a proinflammatory state. Pulpitis is 1 of the most prevalent oral inflammatory diseases. In response to different types of pulpal injury, RCD may occur either in a “single” or an “overlapped mixed” form, including apoptosis, pyroptosis, and NETosis, which can indicate the severity of pulpal inflammation. RCD has received increasing attention because of the cross talk among cell death pathways. Hence, understanding the molecular switch nodes mediating cross talk between diverse RCD pathways may provide new insights into mechanisms underlying cell-fate decision in pulpitis. In this review, we outlined the potential roles of RCD in the progression of pulpitis and some switch nodes connecting different RCD pathways. Ultimately, an in-depth understanding of molecular mechanisms underlying RCD could be translated into effective approaches to preserve pulpal vitality and integrity under pathologic conditions.

Section snippets

Classification of RCD

The NCCD has released 5 guidelines and recommendations dealing with the classification of cell death, which has been recently updated based on morphologic appearance, biochemical features, and functional criteria3. We focused on 4 types of RCD having been identified in pulpitis (ie, apoptosis, pyroptosis, NETosis, and nemesis) and their communication controlling the shift in cell death pathways. Table 1 summarizes 4 RCD modalities and their inhibitors based on NCCD guidelines and recent

Intercommunication between Apoptosis, Pyroptosis, and NETosis

As we learn more about the roles of RCD in pulpitis, it is noteworthy that different RCD signaling pathways are interconnected and even inconvertible. As such, the cross talk of RCD could also be critical for cell fate determination and the extent of pulp inflammation. In the following text, we discuss major nodes between apoptosis, pyroptosis, and NETosis.

Conclusion

Even though great advances have been made in the field of RCD in recent decades, the current knowledge on RCD in pulpitis remains limited. Until recently, researchers have identified apoptosis9, pyroptosis10, and NETosis11 in pulpitis. However, most of the current literature on RCD in pulp inflammation focuses on 1 RCD modality, and it is difficult to identify which types of RCD play the prominent role in the early or late stages of pulpitis, respectively. It is conceivable that the switch

Acknowledgments

Minchun Huang and Chaoning Zhan contributed equally to this study.

Supported by the National Natural Science Foundation of China (grant nos. 81500870 and 81971902) and the Natural Science Foundation of Guangdong Province (grant no. 2016A030313590).

The authors deny any conflicts of interest related to thist study.

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