Signaling Pathway Genetic Variations in Apical Periodontitis

Athira Ajith¹, Usha Subbiah^1*, Deepika. P², Minthami Sharon P²

The purpose of this review is to provide information on host response and genetic variations in major apical periodontitis signaling pathways.

Abstract

Background: Apical periodontitis (AP) is a prevalent infectious disease characterized by inflammation and periradicular tissue loss, primarily induced by endodontic etiological agents. AP is the most common inflammatory lesion affecting teeth in the jaws, involving a complex interplay of cellular and molecular processes. Endogenous mediators, such as prostanoids, kinins, and neuropeptides, play a crucial role in the inflammatory response, which is further influenced by the host's immune response involving cytokines, proteases, and other pro-inflammatory mediators. Methods: This review synthesizes current research on the key signal transduction pathways involved in AP, focusing on the WNT, MAPK, NF-κB, JAK/STAT, and Notch signaling pathways. The genetic basis of AP is also explored, emphasizing the role of gene polymorphisms in disease susceptibility and progression. The review examines the differential expression of signaling molecules in AP tissues and their potential as therapeutic targets to modulate the host response and control disease progression. Results: The WNT/β-catenin pathway is implicated in osteoblast differentiation and bone resorption, with differential expression of WNT proteins observed in AP lesions. The MAPK pathway, particularly p38 MAPK, regulates inflammatory mediators and osteoclastogenesis, contributing to bone resorption in periapical lesions. NF-κB activation is significant in periodontally diseased tissues, and its inhibition has been shown to reduce periapical lesions and angiogenesis. The JAK/STAT pathway, particularly JAK2-STAT3, plays a critical role in immune regulation and cytokine signaling in AP. The Notch signaling pathway is involved in cell differentiation and inflammation, with its activation linked to pro-inflammatory cytokine expression in AP. Conclusion: The review highlights the complexity of the signaling networks involved in AP and the potential for targeting these pathways to modulate the inflammatory response and prevent tissue destruction.

Keywords: Apical periodontitis, Signaling pathways, WNT signaling, Genetic polymorphism, Inflammatory mediators

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